Candidate Gene Polymorphisms Research Articles

Dopamine D2 receptor ANKK1/DRD2 gene (rs18004976) polymorphism and features of the neuroimmune profile in children in North-Eastern and South-Eastern Siberia under exposure to airborne benzo(a)pyrene

Introduction. Examining peculiarities of neuroimmune profiles and candidate gene polymorphism is a relevant trend in identifying markers of effects and sensitivity to chemical exposures in northern areas. Materials and methods. We examined one thousand two hundred fifty three children residing in North-Eastern and South-Eastern Siberia. Blood benzo(a)pyrene levels were detected by HPLC. The ANKK1/DRD2 (rs18004976) gene polymorphism was studied using real-time PCR. IgG to benzo(a)pyrene levels were identified by allergosorbent testing. Dopamine levels were identified by using ELISA. Results. Exposure to airborne benz(a)pyrene in an industrial center in North-Eastern Siberia at the dose of 0.0073 µg/(kg ∙ day) causes an elevated risk of specific hapten hypersensitivity (IgG to benzo(a)pyrene), inhibition of dopaminergic regulation (dopamine deficiency), and elevated benzo(a)pyrene contamination in biological media. The identified changes are similar to those established in children exposed to this polycyclic aromatic hydrocarbon at the dose of 0.0858 µg/(kg ∙ day) in South-Eastern Siberia. Limitations. The sample needs expanding and any results obtained by further observations should be verified. Conclusion. Children exposed to low doses of benzo(a)pyrene (0.0073 µg/(kg ∙ day)) in North-Eastern Siberia have elevated risks of disorders in the neuroimmune profile associated with the T-allele and TT genotype (rs1800497) of the ANKK1/DRD2 gene (OR =2.17 – 2.83, p<0.05) (hyperproduction of IgG to benzo(a)pyrene, dopamine deficiency), which are comparable with similar changes in the neuroimmune profile associated with C-allele and CC-genotype of the ANKK1/DRD2 gene (rs1800497) (OR=1.69 – 1.72, p<0.05) under exposure to benzo(a)pyrene at the dose of 0.0858 µg /(kg ∙ day) in South-Eastern Siberia. This indicates to the higher sensitivity of the body to chemical exposures in specific climatic conditions in northern areas.

Single Nucleotide Polymorphisms and Tendon/Ligament Injuries in Athletes: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis aimed to identify the association between genetic polymorphisms and tendon and ligament injuries in adolescent and adult athletes of multiple competition sports. The PubMed, Web of Science, EBSCO, Cochrane Library, and MEDLINE databases were searched until July 7, 2023. Eligible articles included genetic studies on tendon and ligament injuries and comparisons between injured and non-injured athletes. This review included 31 articles, comprising 1,687 injury cases and 2,227 controls, from a meta-analysis of 12 articles. We identified 144 candidate gene polymorphisms (only single nucleotide polymorphisms were identified). The meta-analyses included vascular endothelial growth factor A (VEGFA) rs699947, collagen type I alpha 1 rs1800012, collagen type V alpha 1 rs12722, and matrix metalloproteinase 3 rs679620. The VEGFA rs699947 polymorphism showed a lower risk of injuries in athletes with the C allele ([C vs. A]: OR=0.80, 95% CI: 0.65-0.98, I 2 =3.82%, p=0.03). The risk of these injuries were not affected by other polymorphisms. In conclusion, the VEGFA rs699947 polymorphism is associated with the risk of tendon and ligament injuries in athletes. This study provides insights into genetic variations that contribute to our understanding of the risk factors for such injuries in athletes.

Adaptive capability of slow-growing backyard poultry as indicated by physiological and molecular responses in a hot and humid coastal climate

Assessing the adaptability of slow-growing rural chickens for improving thermotolerance to suit the global climate change is a major research need. This work was aimed to evaluate the adaptability of CARI-Debendra chickens and to identify the polymorphism as well as expression profiling of thermotolerant genes (HSP70 and GRP78) under prevailing temperature-humidity indices and thermal stress in a coastal environment. One hundred sixty straight run chicks were reared at THI≥75 (control) and THI>80 under coastal climate till 12 weeks. Polymorphism of HSP70 and GRP78 candidate genes were explored using restriction enzymes TaqI and HaeIII to identify possible thermotolerance markers. Expression profiling of both the genes in liver, intestine and pectoralis muscle was determined through quantitative real-time PCR. Rectal and body surface temperature recorded in the neck and back showed significant differences (P < 0.01) with higher temperature in THI>80 group. Comparatively lower live weights (P < 0.05) and poor FCR were recorded in THI>80 group. The villi height in all intestinal segments was significantly lower (P < 0.01), but deeper crypt depth was observed in THI>80 than control group. A lowest thymus weight (P < 0.05) was noted with no significant differences in immune response in treatment group. Serum levels of cholesterol, activities of lactate dehydrogenase, creatinine kinase and concentration of potassium, sodium and thyroxine hormone were not different between the 2 groups. The concentration of triiodothyronine and chloride ion was lower in THI>80 group indicating adaptive changes for thermoregulation. HSP70 gene expressions in the three tissues were differentially increased (P < 0.01) by temperature-humidity indices, but the expression of GRP78 was not different between the 2 groups. The results concluded that the environmental factors interact with genetics on adaptability towards thermotolerance in slow-growing chickens.

Association of candidate gene (INSR & THADA) polymorphism with polycystic ovary syndrome: meta-analysis and statistical power analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that impacts women before reaching menopause. In addition to notable features (irregular ovulation, elevated androgen levels, and the existence of numerous ovarian cysts), individuals with PCOS frequently encounter diverse metabolic, cardiovascular, and psychological conditions. The onset of PCOS is influenced by a combination of factors, and various genetic variations are believed to play a significant role in its progression. The objective of the current study was to explore the link between genetic variations in the candidate genes thyroid-adenoma-associated (THADA) gene and insulin receptor (INSR) and susceptibility to developing PCOS. We conducted an extensive search across various databases, including Google Scholar, PubMed, Science Direct, Scopus, and EMBASE, to compile relevant case-control studies and literature reviews for subsequent statistical analysis. In the present study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, a guideline for Systematic Reviews and Meta-Analysis. While a previous meta-analysis explored the correlation between INSR rs1799817 and THADA rs13429458 and their association with susceptibility to PCOS, our current study did not integrate any findings from these prior investigations. Our research encompassed articles published between 2017 and 2023, and we employed MetaGenyo software to assess the collected data. Statistical power analysis was performed using G*Power 3.1 software. Odds ratios and their corresponding 95% confidence intervals were calculated for each genetic model. Fifteen studies that met the criteria were analyzed. Out of these, ten studies, involving 1,189 cases and 1,005 controls, examined the INSR rs1799817 gene polymorphism, while five studies, including 783 cases and 553 controls, investigated the THADA rs13429458 gene polymorphism. The meta-analysis results indicated that there was no statistically significant association between the INSR rs1799817 gene polymorphism and the risk of PCOS (p>0.05). In contrast, the THADA rs13429458 gene polymorphism showed a significant association with PCOS risk under the over-dominant model (p<0.05). The present meta-analysis demonstrated a notable association between the THADA rs13429458 gene polymorphism and the likelihood of developing PCOS. Further rigorous studies with expanded sample sizes and diverse ethnic representation will be important to comprehensively evaluate and validate these findings.

Understanding molecular mechanisms of vertebral number of variations on Mongolian sheep using candidate genes analysis.

This study aimed to investigate the genetic link between variations in vertebral number and meat production traits, such as body weight and body measurements (body length, body height, heart girth, and shin width) in Mongolian (Bayantsagaan) sheep. Additionally, we examined the association of single-nucleotide polymorphisms (SNPs) in candidate genes, particularly Vertnin (VRTN), Nuclear receptor subfamily 6, group A, member 1 (NR6A1), and synapse differentiation-inducing 1-like (SYNDIG1L), with vertebral number variations and their potential impact on meat production traits. The study involved 220 Bayantsagaan sheep from Bayantsagaan soum, Tov province, Mongolia, including 104 sheep with extra vertebrae group and 116 individuals with typical vertebral number as the control group. Morphological data, including body weight and body measurements, were collected, and genetic samples were obtained. The impact of vertebral number on morphological traits was estimated using a general linear model. SNPs in the VRTN, NR6A1, and SYNDIG1L genes were sequenced, and their association with vertebral number was analyzed using one-way ANOVA. Bayantsagaan sheep with extra vertebrae were, on average, 4.45 kg heavier and exhibited higher variability in body size traits compared to the control group. Four polymorphic sites were identified at the VRTN gene, with one polymorphic locus (VRTN1716) showing a significant association with vertebrae number and body size. Sheep with C/C genotype at VRTN1716 locus, had more vertebrae and larger body size compared to other genotypes. The findings suggest that variations in vertebral number and VRTN gene polymorphisms are linked to favorable meat production traits in Bayantsagaan sheep. The identified SNP (VRTN1716) associated with vertebral number and body size offers the potential for marker-assisted selection in breeding programs. These results provide valuable insights into the genetic basis of meat production traits in Bayantsagaan sheep and may contribute to the development of more efficient breeding strategies.

Genetic polymorphisms and their correlation with dyslipidemia in Chinese patients diagnosed with diabetes mellitus.

Dyslipidemia is a common complication in patients with diabetes mellitus (DM) that increases the risk of cardiovascular disease. Genetic polymorphisms have been implicated in the development of dyslipidemia. To investigate the association between polymorphisms of candidate genes involved in lipid metabolism and dyslipidemia in Chinese patients with DM. A cross-sectional study was conducted on 1098 Chinese patients with DM recruited from multiple healthcare centers. Demographic and clinical data were collected, and dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Genomic DNA was extracted from blood samples and genotyping for selected polymorphisms of candidate genes (APOE, LPL, CETP, and others) was performed using PCR and DNA sequencing techniques. Statistical analyses were performed using logistic regression models adjusted for potential confounding factors. The study population consisted of 578 males (52.6%) and 520 females (47.4%), with a mean age of 58.4 ± 12.2 years. The prevalence of dyslipidemia was 64.8%. Significant associations were found between dyslipidemia and the APOE rs7412 T/T, APOE rs429358 C/C, LPL rs328 G/G, and CETP rs708272 G/G genotypes after adjusting for covariates. Subgroup analyses showed generally consistent associations across subgroups, although some variations in effect sizes were observed. This study identified significant associations between genetic polymorphisms of APOE, LPL, and CETP genes and dyslipidemia in Chinese patients with DM.

Effect of SNPs on Litter Size in Swine.

Although sows do not directly enter the market, they play an important role in piglet breeding on farms. They consume large amounts of feed, resulting in a significant environmental burden. Pig farms can increase their income and reduce environmental pollution by increasing the litter size (LS) of swine. PCR-RFLP/SSCP and GWAS are common methods to evaluate single-nucleotide polymorphisms (SNPs) in candidate genes. We conducted a systematic meta-analysis of the effect of SNPs on pig LS. We collected and analysed data published over the past 30 years using traditional and network meta-analyses. Trial sequential analysis (TSA) was used to analyse population data. Gene set enrichment analysis and protein-protein interaction network analysis were used to analyse the GWAS dataset. The results showed that the candidate genes were positively correlated with LS, and defects in PCR-RFLP/SSCP affected the reliability of candidate gene results. However, the genotypes with high and low LSs did not have a significant advantage. Current breeding and management practices for sows should consider increasing the LS while reducing lactation length and minimizing the sows' non-pregnancy period as much as possible.

Predicting the risk of developing vibration disease and vegetative-sensory polyneuropathy under vibration exposure using analysis of candidate gene polymorphism

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children

BackgroundPlasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children.MethodsBased on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations.ResultsOf 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features.ConclusionTaken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms.

Стан вивчення поліморфізму окремих генів у виникненні бронхіальної астми

The study of the polymorphism of individual genes is the basis of both preventive medicine and is used in the selection of adequate therapy. Polymorphism of individual candidate genes in bronchial asthma (BA) is studied taking into account many personal characteristics and the influence of environmental factors. Aim - to analyze the status of the study of the role of polymorphism of β2-adrenoceptors (ADRβ2) in the pathogenesis of bronchial asthma in children and to compare them with our own findings. Materials and methods. The results of research on polymorphism of individual genes in children with BA, which includes the PubMed database, were analyzed. An in-depth study of the anamnesis data (disease, life, hereditary), a complex clinical and laboratory examination of children (n=101) of school age with BA was carried out (the average age was: for boys 11.15±0.48 years; for girls - 10.63±0.7 years). Patients were diagnosed with BA in accordance with the GINA recommendations of the current revision. Determination of the Arg16Gly polymorphism of the ADRβ2 gene (rs 1042713) was performed by the polymerase chain reaction method followed by restriction enzyme analysis. The obtained data were processed in the Statsoft STATISTICA software package. Mean values were given as (M±m), Student's test was used for comparison. Results. The assessment of the frequency of polymorphism of the Arg16Gly gene in BA established that two variants prevailed in boys: Arg16Gly and Gly16Gly; at that time, the Gly16Gly genotype prevailed among girls, which, according to individual studies, is associated with good effectiveness of the applied therapy (nebulization of salbutamol). Mutations in the ADRβ2 gene in patients with BA were twice as frequent in the Arg16Gly genotype and three times as frequent in the Gln27Glu genotype, in contrast to healthy children. Such a polymorphism affects the functional activity of ADRβ2, the occurrence and course of BA. Conclusions. The Arg16Gly polymorphism of the ADRβ2 gene in children with BA largely determines the sensitivity of ADRβ2 to the applied exacerbation therapy and the effectiveness of basic treatment. In patients with the Gly16Gly genotype, most researchers note the good clinical effectiveness of both fast broncholytic drugs (β2 short-acting agonists) and basic anti-inflammatory drugs. The diagnosed homozygous Arg16Arg genotype of the ADRβ2 gene mostly accompanies the uncontrolled (or partially controlled) course of asthma in children. The revealed features of the Arg16Gly polymorphism of the ADRβ2 gene will help the doctor to draw up an adequate treatment plan, which is based on the genetically determined sensitivity of ADRβ2 receptors to medical preparations. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Аналіз перинатальних наслідків у жінок із загрозою невиношування вагітності в першому триместрі залежно від факту утворення ретрохоріальної гематоми

Purpose - to evaluate the effectiveness of the developed personalized approach to the management of patients with a threat of miscarriage in the first trimester depending on the fact of the formation of a retrochorial hematoma (RCH) in order to prevent the occurrence of preeclampsia (PE) in them. Materials and methods. A prospective analysis of the course of pregnancy and childbirth was conducted in 137 women with a threat of pregnancy aged from 20 to 47 years (the Group I - 60 patients with RCH, the Group II - 77 patients with a threat of termination of pregnancy without hematoma). Bibliosemantic analysis was used in the study; estimated anthropometric data; an enzyme-linked immunosorbent assay was performed to study hormone levels; polymerase chain reaction was used to determine polymorphisms of thrombophilia and angiogenesis genes; instrumental - to assess the condition of the fetus (ultrasound diagnosis of the fetus with Doppler blood flow of the umbilical artery, uterine arteries, middle cerebral arteries, non-stress test). Results. The average age of women of the Group I was 31.2±0.6 (95% CI: 30.0-32.4) years, of the Group II - 32.2±0.6 (95% CI: 31.0-33.3) of the year (p=0.243 according to the t-criterion). According to the Alberta Perinatal Health Program (APHP) adapted perinatal risk scale, 21 (35.0%) and 36 (46.7%) patients were assigned to the low perinatal risk group, respectively, and 30 (50.0%) medium risk) and 32 (41.5%) women, and to the high-risk group - 9 (15.0%) and 9 (11.7%) at p&gt;0.05. During the treatment and observation of women with a threat of miscarriage in the first trimester, the developed treatment algorithm was followed: stabilization of the hematoma, reduction of myometrial tone, hormonal support of pregnancy with further determination of the need for the use, dose and duration of low-molecular-weight heparin (LMWH) in combination with aspirin. Differences between the Groups I and II revealed by means of a comparative analysis made it possible to outline the clinical and anamnestic factors that can serve as predictors of the development of PE in women with RCH. Conclusions. The occurrence of RCH at the stage of early placentation increases the risks of developing placental dysfunction and obstetric complications related to it. The early appointment of aspirin (up to 12 weeks) in women with a high risk of developing PE allows to reduce the synthesis of platelets and thromboxane while preserving the synthesis of prostacyclin in the vascular wall in the initial stages of placentation. The combination of aspirin with the use of LMWH in women with the presence of genetic polymorphisms of candidate genes for thrombophilia and angiogenesis prevents the delay in the onset of uteroplacental circulation and promotes full placentation. A personalised approach to the management of pregnancy in women with a threat of termination due to the formation of RCH in the first trimester of pregnancy has made it possible to improve perinatal outcomes in the management of this category of pregnant women. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Immunological and genetic profile of the pediatric population in the nitrate geochemical province

BACKGROUND: Contamination of groundwater with nitrates may result in substantial adverse effects on the health of various population groups.&#x0D; AIM: To study the immune status and genetic profile of children residing in the nitrate geochemical province in the Perm Region.&#x0D; MATERIAL AND METHODS: We conducted a study on a total of 78 preschool children residing in areas with varying levels of nitrate in the underground drinking water sources. The children were divided into two groups for comparison purposes. The first group consisted of 43 children who consumed drinking water that met the acceptable standards for nitrate content. The second group comprised 35 children who consumed drinking water with elevated levels of nitrates. To assess the impact of nitrate content on the children’s health, several measurements were taken. Firstly, the level of nitrates in the household drinking water was analyzed. Additionally, the concentration of N-nitrosamines and nitrate ions in the children’s urine, was determined. To evaluate the immunoregulation parameters, the technology of flow cytometry and enzyme immunoassay were employed, along with PCR to examine genetic polymorphisms.&#x0D; RESULTS: A statistically significant difference (p 0.001) was observed in the nitrate content of drinking water between the observation area and the comparison area, with the former showing levels 2.8 times higher. Furthermore, children in the observation group exhibited a significant increase (p 0.05) of 2.3 times in N-nitrosodiethylamine content and 1.6 times in nitrate ion concentration in their urine compared to children in the comparison group. In addition, the observation group displayed a significant decrease (p 0.05) in the number of NKT cells and an increase in the levels of CD3+CD25+-, CD3+CD95+-cells, bax, IL-17, Annexin V-FITC+PI–-, and Annexin V-FITC+PI+-lymphocytes, when compared to the results obtained from the comparison group. Moreover, the presence of polymorphisms in candidate genes associated with tumor formation (CYP1A1 (rs1048943), MMP9 (rs17576), PPARD (rs2016520), BRCA1 G/A (rs3950989)) was also identified.&#x0D; CONCLUSION: Our results suggest that children who are exposed to chronic low-levels of nitrates (at a concentration of 1.2 MPC) through drinking water from underground sources exhibit an excessive presence of N-nitrosodiethylamine and nitrate ions in their urine. These findings, in conjunction with the genetic profile of genes responsible for tumor formation, influences the characteristics of the immune response.

Genetic determinants of taxane-induced peripheral neuropathy.

The efficacy of taxane‑containing regimens has been demonstrated for various cancers, particularly ovarian, endometrial, breast, lung, and prostate cancers. However, extensive taxane-induced toxicities limit their use. Prediction and management of many toxic complications in cancer patients have evolved significantly over the last decade. Peripheral neuropathy is the most typical non-hematological taxane-related complication, and it has amultifactorial pathogenesis. It is often dose-dependent and progressive during therapy and sometimes even after treatment. Unfortunately, the prediction of these common adverse events remains unclear. In the past few years, several polymorphisms of candidate genes with apossible role in the development of this consequence were studied. This minireview aims to highlight the critical yet underappreciated roles of genetic predictors that may increase susceptibility to taxane-induced peripheral neuropathy in cancer patients (Ref. 40). Keywords: taxanes, paclitaxel, docetaxel, peripheral neuropathy, risk factors, genetic polymorphisms.

Genetic profile and association of candidate gene polymorphism with productivity of Kalmyk cattle

The research was carried out in the laboratory of molecular genetic examination of the RNPC on reproduction of farm animals of the KalmSU named after B. B. Gorodovikov. The purpose of the research was to study the genetic profile and identify the influence of polymorphic candidate genes on the selection and breeding qualities of Kalmyk breed cattle. Analysis of these results by PCR-PDRF of Kalmyk bulls by the Tg locus revealed that 31% of 80 animal heads were carriers of the TT genotype associated with desirable traits, according to the GH locus in the breeding reproducer “Plodovitoye” revealed that 44% of 86 animals were carriers of the VV genotype associated with desirable economic characteristics and valuable qualities. This can be explained by the purposeful conduct of breeding work on breeding indicators in farms. Carriers of the VV genotype exceed their peers in the TT genotype by 9.1 kg (P&gt;0.95). Based on the results obtained, it can be assumed that GH polymorphism has a positive effect on the meat productivity of Kalmyk bulls in comparison with TG.

Genetic Polymorphisms Associated with Metabolic Syndrome in North Africa: Systematic Review and Meta-Analysis

Background: Metabolic syndrome (MetS) is a multifactorial disorder characterized by the aggregation of various metabolic disorders, including obesity, hyperglycemia, hypertriglyceridemia, hypoHDLemia and hypertension. In addition to environmental influences, genetic factors can play a major role in the development of MetS. Objective: The present bibliographic review aims to examine the contribution of candidate gene polymorphisms to MetS susceptibility in North African populations. Methods: A systematic review search was conducted to identify pertinent articles published on Embase, PubMed, and Web of Science from their inception to August 2, 2023 to obtain all reported genetic data related to MetS in North African populations. Results: According to the literature search strategy, 785 articles were initially obtained from the cited databases, and 15 more papers were found utilizing other sources. Following the filtering procedure, 25 papers totalising 3925 cases and 4431 controls were included, from which only 13 were eligible for meta-analysis. The meta-analysis results suggest that the genetic cumulative risk of developing MetS was substantially influenced by four polymorphisms, including APOA5 (rs3135506 and rs662799), APOC3 (rs5128), and FTO (rs9939609), while the vaspin polymorphism (rs2236242) was reported to play a protective role from MetS. Furthermore, no significant association was observed between rs1169288, rs2464196, and rs735396 polymorphisms at HNF1A gene and MetS development. A narrative synthesis of association studies revealed that a multitude of candidate genes is associated with MetS components. In all included studies, 14 polymorphisms were linked to obesity, and 13 polymorphisms were associated with hyperglycemia. The association of hypertension with polymorphisms represents the lowest number, with only seven polymorphisms associated with this MetS component. In the other hand, studies about MetS in North Africa considering the genetic association of candidate genes with dyslipidemia component represents the highest number with 20 polymorphisms in approximately 14 genes. Conclusion: The present meta-analysis suggests that four polymorphisms, namely rs3135506 and rs662799 at APOA5 gene, rs5128 at APOC3 and rs9939609 at FTO, contributed significantly to the MetS risk susceptibility, via their association with some MetS components as dyslipidemia, hyperglycemia, obesity, and hypertension. Nevertheless, we can state that genetic association and genetic susceptibility studies to MetS in North African populations are still lacking, requiring additional well-designed epidemiogenetic studies.

New Insights into Polymorphisms in Candidate Genes Associated with Incidence of Postparturient Endometritis in Ossimi Sheep (Ovis aries)

This study examined the genes related to immunity, metabolism, and antioxidants that may interact with the prevalence of postpartum endometritis in Ossimi sheep. We used fifty endometritis-positive Ossimi sheep and fifty that appeared to be normal. For the purpose of taking blood samples, each ewe had its jugular vein pierced. Nucleotide sequence differences for the immunological (alpha-2-macroglobulin, toll-like receptor 2, transforming growth factor beta, interleukin 1 receptor-associated kinase 3, high-mobility group box 1, Fc alpha and Mu receptor, and inducible nitric oxide synthase), metabolic (ADAM metallopeptidase with thrombospondin type 1 motif 20, potassium sodium-activated channel subfamily T member 2, Mitogen-activated protein kinase kinase kinase 4, FKBP prolyl isomerase 5, and relaxin family peptide receptor 1), and antioxidant (superoxide dismutase, catalase, NADH: ubiquinone oxidoreductase subunit s5, and Heme oxygenase-1) genes were found among sheep with endometritis and those in good condition utilizing PCR-DNA sequencing. Fisher’s exact test revealed a significant difference in the probability of dispersal of all significant nucleotide changes between ewe groups with and without endometritis (p ˂ 0.01). In endometritis ewes, there was a considerable up-regulation of the expression levels of A2M, TLR2, IRAK3, HMGB1, FCAMR, iNOS, ADAMTS20, KCNT2, MAP3K4, FKBP5, RXFP1, and HMOX1. Conversely, there was a down-regulation of the genes that encode TGF-β, SOD, CAT, and NDUFS5. The kind of marker and its frequency in postparturient endometrtits significantly impacted the transcript levels of the indicators under analysis. The results validate that nucleotide changes and gene manifestation outlines in these candidates are significant predictors of the prevalence of endometritis in sheep.

Pharmacogenetic Factors of Clozapine-Induced Metabolic Syndrome

(1) Introduction: Despite modern therapies, approximately 20-30% of patients with schizophrenia remain resistant to psychopharmacotherapy. Clozapine is the only antipsychotic with proven efficacy for treatment resistance in schizophrenia (TRS). The most common adverse drug reaction (ADR) during clozapine administration are metabolic disturbances, particularly metabolic syndrome (MS). Because MS leads to a twofold increase in mortality from cardiovascular disease and a 1.5-fold increase in mortality from all causes, and clozapine is often the only treatment option for TRS, it is critical to monitor and management metabolic abnormalities. The high interindividual differences in the development of clozapine-induced MS suggest that genetic factors may play an important role. (2) Purpose: The aim of this study was to identify relevant single nucleotide polymorphisms (SNPs) of candidate genes for clozapine-induced MS, because based on these data, a genetic risk panel can be constructed to assess the likelihood of developing clozapine-induced MS in patients with schizophrenia. (3) Materials and Methods: We searched for full-text publications in PubMed, Web of Science, Springer, Google Scholar, and electronic libraries in English and Russian, available from inception to 30 October 2023. Keywords were the following: metabolic disturbances, clozapine, metabolic syndrome, schizophrenia, genes, adverse drug reactions, antipsychotics, pharmacogenetics, genetic biomarker, single nucleotide variant, polymorphism, association, variation, and metabolic syndrome genes. (4) Results: we included 6 naturalistic cross-sectional open-label trials, included patients with schizophrenia, schizoaffective, schizophreniform disorder or psychotic disorder, who were treated with first and second generations antipsychotics, among which there was also clozapine and 1 meta-analysis which reviewed association between HTR2C gene polymorphisms and anti-psychotic-induced MS in schizophrenia patients. According to the results of our scoping review the carriage of SNPs in the studied candidate genes associated with clozapine-induced MS are the following: 1) CYP1A2 gene: genotype AA of rs762551 (NG_008431.2:g.32035C&gt;A); 2) CYP2C19 gene: CYP2C19*2 polymorphism; 3) HTR2C gene: genotype CC of rs518147 (NM_000868.2:c.-697G&gt;C), minor allele C of rs1414334 (NG_012082.3:g.324497C&gt;G), genotype CC of rs518147 (NM_000868.2:c.-697G&gt;C), genotype GG of rs12836771 (NG_012082.3:g.71829A&gt;G); 4) LEP gene: genotypes AG and GG of rs7799039 (NG_044977.1:g.475G&gt;A); 5) LEPR gene: genotypes AG and GG of rs1137101 (NG_015831.2:g.177266A&gt;G). (4) Conclusions: Uncovering the genetic biomarkers of clozapine-induced MS may provide a key to developing a strategy for the personalized prevention and treatment of this ADRs of clozapine in patients with schizophrenia spectrum disorders in real clinical practice.

Features of neuroimmune and genetic profile in men with clinical manifestations of vegetative vascular dystonia of hypertensive type

Background. Identification of immune, neurohumoral and genetic markers of vegetative vascular dystonia of the hypertensive type is relevant in the aspect of prevention and early diagnosis of cardiovascular pathology in middle-aged men.&#x0D; Aim. To study the features of the immune and neurohumoral profile in middle-aged men with clinical manifestations of vegetative vascular dystonia of the hypertensive type, associated with polymorphic variants of candidate genes for blood vessel tone regulation.&#x0D; Material and methods. 113 middle-aged men (mean age 46.13.9 years) were examined. The observation group included 65 men (average age 45.34.6 years) with clinical manifestations of vegetative vascular dystonia of the hypertensive type. The comparison group included 48 men without signs of autonomic regulation dysfunction (average age 48.33.2 years). The groups were comparable in age (p=0.593), ethnic and social composition. The content of CD3+CD95+ lymphocytes was determined by flow cytometry; interleukin-6, total immunoglobulin E, adrenaline, serotonin by enzyme immunoassay. Polymorphic variants of the genes ADRB2 (rs1042713), ADD1 (rs4961), GNB3 (rs5443), HTR2A (rs7997012) were identified by real-time polymerase chain reaction. Statistical processing: comparison of arithmetic means using Student's t-test or MannWhitney U-test, calculation of odds ratio (OR) and 95% confidence interval (CI).&#x0D; Results. The immune profile of men with disorders of autonomic regulation was characterized by a deficiency of CD3+CD95+ lymphocytes against the background of overproduction of total immunoglobulin E and interleukin-6. The neurohumoral profile was characterized by excessive synthesis of adrenaline and serotonin. The development of symptoms of vegetative vascular dystonia of the hypertensive type was associated with the G allele of the ADRB2 gene (rs1042713) (OR=1.80; 95% CI=1.053.08; p 0.05), the G allele of the ADD1 gene (rs4961) (OR=3.51; 95% CI=1.279.67; p 0.05), C allele of the GNB3 gene (rs5443) (OR=2.30; 95% CI=1.214.37; p 0.05), A allele of the HTR2A gene (rs7997012) (OR=2.38; 95% CI=1.374.15; p 0.05).&#x0D; Conclusion. Changes in the immune profile were identified (deficiency of CD3+CD95+ lymphocytes, excess of total immunoglobulin E, interleukin-6), associated with hyperproduction of adrenaline and serotonin against the background of polymorphism of candidate genes for vascular tone regulation [ADRB2 (rs1042713), ADD1 (rs4961), HTR2A (rs7997012 ), GNB3 (rs5443)].

Influence of polymorphisms in candidate genes on carcass and meat quality traits in rabbits.

Candidate gene is a powerful approach to study gene-trait association and offers valuable information for genetic improvement using marker-assisted selection. The current work aimed to study the polymorphisms of four single nucleotide polymorphism (SNPs) at located growth hormone (GH), insulin-like growth factor-II (IGF-II), fat mass and obesity-associated (FTO), and insulin receptor substrate-1 (IRS-1) genes, and their association with the carcass, and meat quality traits in rabbits. The SNPs were genotyped using RFLP-PCR in New Zealand White and local Baladi rabbits. The results revealed that the heterozygous genotype was the most frequent in all cases, except for the FTO SNP in LB rabbits. There was a significant effect for GH genotypes on meat lightness after slaughter and hind-part weight. While, IGF-II mutation significantly affected slaughter, hot carcass, commercial carcass, and hind-part weights. The FTO SNP was associated with cooking loss and intramuscular fat weight, and the IRS-1 SNP was significantly associated with drip loss and intramuscular fat. Specific-breed effects were obtained for IGF-II SNP on cooking loss, and for the intramuscular fat. Although the results suggested that these mutations are useful candidate genes for selection, more research for detecting more variants associated with carcass and meat quality traits in rabbits are recommended.

Candidate gene polymorphisms are linked to dispersive and migratory behaviour: Searching for a mechanism behind the "paradox of the great speciators".

The "paradox of the great speciators" has puzzled evolutionary biologists for over half a century. A great speciator requires excellent dispersal propensity to explain its occurrence on multiple islands, but reduced dispersal ability to explain its high number of subspecies. A rapid reduction in dispersal ability is often invoked to solve this apparent paradox, but a proximate mechanism has not been identified yet. Here, we explored the role of six genes linked to migration and animal personality differences (CREB1, CLOCK, ADCYAP1, NPAS2, DRD4, and SERT) in 20 South Pacific populations of silvereye (Zosterops lateralis) that range from highly sedentary to partially migratory, to determine if genetic variation is associated with dispersal propensity and migration. We detected genetic associations in three of the six genes: (i) in a partial migrant population, migrant individuals had longer microsatellite alleles at the CLOCK gene compared to resident individuals from the same population; (ii) CREB1 displayed longer average microsatellite allele lengths in recently colonized island populations (<200 years), compared to evolutionarily older populations. Bayesian broken stick regression models supported a reduction in CREB1 length with time since colonization; and (iii) like CREB1, DRD4 showed differences in polymorphisms between recent and old colonizations but a larger sample is needed to confirm. ADCYAP1, SERT, and NPAS2 were variable but that variation was not associated with dispersal propensity. The association of genetic variants at three genes with migration and dispersal ability in silvereyes provides the impetus for further exploration of genetic mechanisms underlying dispersal shifts, and the prospect of resolving a long-running evolutionary paradox through a genetic lens.