Association Of Polymorphisms Research Articles

Association of genetic polymorphism of interleukin 1-alpha and interleukin 1-beta with external apical root resorption in orthodontic patients

Objective > To assess the allele rs 1143634 in IL-1β and rs1800587 in IL-1α in patients for orthodontically induced external apical root resorption (EARR).Material and methods > Intra-oral periapical radiograph (IOPA) of maxillary incisors of 142 Patients were evaluated for resorption at two time points; before the start of fixed mechanotherapy (T1) and after one year of treatment (T2). The individuals with root resorption< 2mm were categorized as a control group(Group 1; n=90), and resorption >2mm were categorized as case group (Group 2; n=52). Buccal swabs of all patients were taken and DNA could be isolated in 95 out of 142 samples (group 1 {n=58}, group 2 {n=37}) which were then screened for the selected two polymorphic targets to determine the nucleotide status of these targets. Tetra-primer ARMS PCR reactions were carried out using all 4 primers for each polymorphism.Results > rs11800587 was not associated with risk of EARR in any inheritance model. Chi-square test for association of alleles with EARR revealed that rs1143634 was associated with the risk of EARR in an allelic model in such a way that A allele of this SNP increased the risk of EARR 4 folds [OR = 4.375; p=0.016]. However, the adjusted level of significance using the Holm-Bonferroni method for rs1143634 was p<0.010 for A and G comparison rendering the results non-significant.Conclusion > SNP rs1143634 and SNP rs11800587 were not associated with risk of EARR in any inheritance model.

Risk of Cardiovascular Complications Among Type 2 Diabetes Mellitus Patients with GSTP1 Genetic Polymorphism: A Nested Case-Control Study and Docking Studies.

The genetic alteration in the antioxidant gene Glutathione-S-Transferases Pi 1 (GSTP1) namely GSTP1*IIe105Val (rs1695) and GSTP1*Ala114Val (rs1138272) changes the individual susceptibility to cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) by altering the substrate binding and catalytic activity. This study aims to investigate the association of GSTP1 rs1695 and rs1138272 polymorphism with CVD development in T2DM patients. Genotyping was performed with 400 study participants-group I: control; group II: T2DM; group III: CVD; and group IV: T2DM/CVD [n = 100 each] by PCR-RFLP. The rs1695 and rs1138272 polymorphism were docked against NPACT and NUBBE database and virtually screened using glide. The study reported that rs1695 polymorphism was associated with T2DM risk under dominant and allelic genetic models [OR = 1.97(1.08-3.59) p = 0.02 and OR = 1.79(1.20-2.66) p = 0.003, respectively]. The val/val genotype, dominant, recessive model, and T allelic genetic model were associated with increased CVD risk [OR = 4.15(1.97-8.73) p = < 0.01; OR = 3.16(1.65-6.04) p = < 0.01; OR = 3.47(1.91-6.31) p = < 0.01; and OR = 2.94(1.95-4.43) p = < 0.01, respectively]. In contrast, rs1695 polymorphism was not associated with CVD development among patients with T2DM. In rs1138272, the wild genotype was only detected and neither heterozygous nor val/val genotype was observed. The docking analysis revealed that the Ile105Val mutation plays a significant role in altering the GSTP1 capacity compared to the Ala115Val mutation. This suggests that the Ile105Val mutation has a greater impact on the protein's structure, function, or susceptibility to diseases compared to the Ala115Val mutation. In summary, genetic alteration in GSTP1 rs1695 potentially contributes to an increased risk of T2DM and CVD.

Association of ADIPOQ Gene Polymorphisms with Type 2 Diabetes and Obesity Risk in the Kazakh Population: A Case–Control and Population-Based Study

Type 2 diabetes mellitus (T2DM) is a socially significant disease with increasing prevalence worldwide. It is characterized by heterogeneous metabolic disorders and is associated with various risk factors, including BMI, abnormal lipid levels, hypertension, smoking, dietary preferences, physical inactivity, sedentary lifestyle, family history of diabetes, prediabetes or gestational diabetes, inflammation, intrauterine environment, age, sex, ethnicity, and socioeconomic status. Assessing the genetic risk of developing T2DM in specific populations remains relevant. The ADIPOQ gene, encoding adiponectin, is directly related to the risk of developing T2DM, obesity, and cardiovascular diseases. Our study demonstrated significant associations of ADIPOQ gene polymorphisms with the risk of developing T2DM and obesity, as well as with fasting glucose levels and BMI, in the Kazakh population. Specifically, rs266729 was significantly associated with T2DM and obesity in the Kazakh population, while other studied polymorphisms (rs1501299, rs2241766, and rs17846866) did not show a significant association. These findings suggest that ADIPOQ gene polymorphisms may influence T2DM risk factors and highlight the importance of genetic factors in T2DM development. However, further research in larger cohorts is needed to confirm these associations.

#1861 Association of the polymorphisms of the angiotensin converting enzyme and FRMD3 genes in the development of diabetic kidney disease

Abstract Background and Aims Individual genetic biomarkers, called single nucleotide polymorphisms (SNPs), have been proposed that could represent potential non-invasive markers for the early diagnosis of diabetic kidney disease (DKD), in addition to their association with a characteristic phenotype. Aim To determine the association of polymorphisms of the Angiotensin Converting Enzyme and FRMD3 genes with the risk of developing ERD in patients with type 2 diabetes. Method Case-control study, comparative, observational, ambispective and cross-sectional, in which men and women, over 18 years of age with T2D with and without ERD and healthy patients, who underwent DNA extraction, participated. genomic and subsequent genotyping, and detection of SNPs by mass spectrometry. Results A total of 400 patients participated, 199 men and 201 women, within which they were divided into three groups: 100 patients with type 2 diabetes and ERD confirmed by renal biopsy, 100 patients with type 2 diabetes without ERD and 200 healthy controls. A total of 3 polymorphisms of the ACE and FRMD3 genes were studied. Among the polymorphisms analyzed in the logistic regression, rs179975 CA (OR, 6.2; 95% CI: 1.15-7.48, p = 0.03), rs1888747 GA (OR, 6.6; 95% CI: 4.60-8.45, p = 0.002) and rs10868025 resulted. CG (OR, 4.1; 95% CI: 2.40-5.60, p = 0.002) Table 1. Conclusion Our study demonstrated the association of well-established genetic variants of the ACE and FRMD3 gene polymorphisms with the presence of ERD, showing that these SNPs, specifically rs179975 CA, rs1888747 GA and rs10868025 GC, may represent important genetic markers in the development of ERD and could be a predisposing factor due to the high frequency and strength of association that were observed in our studied population, this being the first study in Latin America.

Genetic Association of Interleukin 16 Gene Polymorphisms (rs11556218 & rs4778889) with Type 1 Diabetes in Egyptian Children: A Case-Control Study

ABSTRACT Background Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the underlying reason for the onset of T1D is unknown, due to their effector and regulatory roles in immune responses, cytokines are essential in developing autoimmune disorders. Interleukin (IL)16 is an immunomodulatory cytokine implicated in several inflammatory and autoimmune diseases. Objective This study was designed to examine the association of IL16 gene polymorphisms, rs11556218 T > G and rs4778889 T > C, with the risk of T1D in Egyptian children. Methods Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, we analyzed rs11556218 T > G and rs4778889 T > C polymorphisms of the IL16 gene in 100 T1D subjects and 93 controls. Results Rs11556218 T > G polymorphism of the IL16 gene was not associated with the risk of developing T1D. Analysis of IL16 gene rs4778889 T > C showed that the TT genotype had a considerably higher risk of T1D than the TC genotype [OR = 2.195 (1.205–3.999)]. In comparison to patients with the C allele [OR = 0.6914 (0.38–1.2569)], patients with the T allele [OR = 1.45 (0.7956–2.6296)] were notably more likely to have T1D. A significant decrease was found in the frequency of GT (OR = 0.43, p = .03) and TC (OR = 0.32, p = .011) haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms in T1D patients compared with controls. Conclusion IL16 gene rs4778889 T > C polymorphism might be associated with susceptibility to T1D. Egyptians with TT genotypes are more likely to develop T1D. However, GT and TC haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms highlight their protective role againstT1D disease.

Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia

To investigate the association between three selected pain polymorphisms and clinical, functional, sensory-related, psychophysical, psychological or cognitive variables in a sample of women with fibromyalgia (FMS). One hundred twenty-three (n = 123) women with FMS completed demographic (age, height, weight), clinical (years with pain, intensity of pain at rest and during daily living activities), functional (quality of life, physical function), sensory-related (sensitization-associated and neuropathic-associated symptoms), psychophysical (pressure pain thresholds), psychological (sleep quality, depressive and anxiety level) and cognitive (pain catastrophizing, kinesiophobia) variables. Those three genotypes of the OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 single nucleotide polymorphisms were obtained by polymerase chain reactions from no-stimulated whole saliva collection. No significant differences in demographic, clinical, functional, sensory-related, psychophysical, psychological and cognitive variables according to OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680 genotype were identified in our sample of women with FMS. A multilevel analysis did not either reveal any significant gene-to-gene interaction between OPRM1 rs1799971 x HTR1B rs6296, OPRM1 rs1799971 x COMT rs4680 and HTR1B rs6296 x COMT rs4680 for any of the investigated outcomes. This study revealed that three single nucleotide polymorphisms, OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680, mostly associated with chronic pain were not involved in phenotyping features of FMS. Potential gene-to-gene interaction and their association with clinical phenotype in women with FMS should be further investigated in future studies including large sample sizes.

Association of Polymorphism with Periodontitis and Salivary Levels of Hypoxia-Inducible Factor-1α.

This investigation aims to investigate the association between HIF-1α genetic polymorphism and periodontitis and examine and contrast the levels of HIF-1α present in the saliva of subjects afflicted with periodontitis and in the control group. Additionally, this study aims to establish diagnostic proficiency of this biomarker in distinguishing between periodontal health and disease. This study entailed the collection of venous blood samples and unstimulated saliva samples from a total of 160 participants, encompassing 80 individuals diagnosed with periodontitis and 80 periodontitis-free individuals. The periodontal parameters were evaluated, involving the measurement of clinical attachment loss, the probing pocket depth, and the bleeding on probing percentage. Subsequently, genetic analysis of HIF-1α using polymerase chain reaction (PCR) technique, DNA sequencing, and enzyme-linked immunosorbent assays was conducted. The genetic analysis of 352 bp of the HIF-1α gene revealed the presence of 66 single-nucleotide polymorphisms (SNPs) in control samples, whereas 78 SNPs were found in periodontitis sample. The nucleotide A was replaced with a C nucleotide at position 207 of the amplified PCR fragments. The homozygous AA pattern was predominant in the control group, with significant differences between the two groups. In contrast, the homozygous CC pattern was more dominant in the periodontitis group, with significant differences between the two groups. The analysis of Hardy-Weinberg equilibrium for the comparison between the observed and the expected genotypes showed significant differences between the observed and the expected values in the control and periodontitis groups, as well as the total sample. The highest mean values of the measured periodontal parameters were found in the periodontitis group (clinical attachment loss = 4.759, probing pocket depth = 4.050, and bleeding on probing = 30.950) with statistically significant differences between the groups. The periodontitis group showed significantly higher salivary HIF-1α levels compared to control group (p < 0.001). Besides, HIF-1α is a good biomarker in distinguishing between periodontal health and periodontitis. rs1951795 SNP of HIF-1α has no significant impact on the progression of periodontitis and the salivary level HIF-1α. Periodontitis results in a notable elevation in HIF-1α salivary levels, with an outstanding diagnostic ability to distinguish between periodontitis and periodontal health.

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients.

A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.

Association of BDNF polymorphism with gestational diabetes mellitus risk: a novel insight into genetic predisposition.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy with potential long-term health implications for the mother and child. The interplay between genetics and GDM susceptibility remains an area of active research. Recently, brain-derived neurotrophic factor (BDNF) was investigated in relation to obesity and impaired glucose metabolism and pathogenesis. We aimed to investigate the association of common BDNF polymorphisms, with GDM risk in Israeli females. A cohort of 4,025 Israeli women data for BDNF common SNPs was analyzed for potential association with GDM using binary logistic regressions analysis (SPSS 29.0 and R) adjusted for confounding variables (age, T1DM, T2DM, PCOS) under different genetic models. The GDM and Non-GDM genetic frequencies for the BDNF rs925946 Tag-SNP were significantly different. The genetic frequencies were 54.16 %, and 66.91 % for the wild type (GG), 38.88 and 29.64 % for the heterozygotes (TC), and 6.94 and 3.48 % for the risk allele homozygotes (TT) for the GDM non-GDM populations, respectively. Carriers of BDNF rs925946 were significantly associated with higher risk for GDM, following the dominant genetic model (OR=1.7, 95 % CI 1.21-2.39, p=0.002), the recessive genetic model (OR=2.05, 95 % CI 1.04-4.03, p=0.03), and the additive genetic model (OR=1.62, 95 % CI 1.13-2.3, p=0.008). This association persisted after adjusting for age, T1DM, T2DM, and polycystic ovary syndrome (PCOS). Carrying BDNF rs925946 polymorphism predisposes to a higher risk of GDM pathogenesis. Its role and implications warrant further investigation, especially when considering preventive measures for GDM development.

Evaluation of genetic polymorphisms in TNF‑α‑308G/A rs1800629 associated with susceptibility and severity of rheumatoid arthritis: A systematic review and meta‑analysis.

To investigate the association of gene polymorphisms of TNF-α-308G/A rs1800629 with the susceptibility and severity of rheumatoid arthritis (RA), literature from PubMed, EMBASE, Web of Science and CNKI databases was searched. Two authors screened the literature independently, extracted data and evaluated the risk of bias of the included studies. According to the inclusion and exclusion criteria, five genetic models were established: The allelic model (A vs. G), dominant model (GA + AA vs. GG), recessive model (AA vs. GG + GA), co-dominant model (AA vs. GG) and super-dominant model (GG + AA vs. GA). Stata 17.0 software was used for the meta-analysis. A total of 34 eligible studies with 12,611 subjects were included, including 6,030 cases in the RA group and 6,581 controls. Meta-analysis calculations revealed that the genetic polymorphisms of TNF-α-308G/A rs1800629 were not significantly associated with susceptibility to RA, with an odds ratio and 95% confidence interval (CI) for each genetic model [A vs. G: 0.937 (0.762-1.152); GA + AA vs. GG: 0.918 (0.733-1.148); AA vs. GG + GA: 1.131 (0.709-1.802); AA vs. GG: 1.097 (0.664-1.813); and GG + AA vs. GA: 1.108 (0.894-1.373)]. For the association between TNF-α-308G/A rs1800629 gene polymorphisms and the severity of RA, the results of subgroup analysis calculations showed that TNF-α-308G/A rs1800629 gene polymorphisms were associated with the severity of RA in European populations, with the gene model and 95% CI [GA + AA vs. GG: 0.503 (0.297-0.853); and GG + AA vs. GA: 2.268 (1.434-3.590)]. When assessing the confidence in the positive results of the present study through the false-positive report probability, the positive results were observed to be reliable. No significant association was observed between genetic polymorphisms in TNF-α-308G/A rs1800629 and susceptibility to RA. However, a significant association exists with the severity of RA in European populations.

GATA genotype and FY*B(-67T&gt;C) polymorphism as a cheap and reliable tool to evaluate ethnicity in Brazilian patients submitted to autologous transplantation

Abstract Collecting high quality data on race and ethnicity is crucial for clinical research, notably in genetic association studies, to avoid confounding by different ethnic background among patients, a bias referred to as population stratification. In Brazil, to describe race we commonly use the National Institute of Geography and Statistics (IBGE) classification, so-called “self-declared color”, but it is acknowledged that defining ancestry by phenotypic characteristics, especially in countries with highly mixed population like Brazil, can be misleading. We aimed to evaluate the relationship between the GATA FY*B(-67T&gt;C) polymorphism and self-declared race in Brazilian patients undergoing autologous transplantation and verify the feasibility of using this test as a more reliable tool to evaluate ethnicity in this population. Methods: We conducted a study to evaluate the association of candidate-gene polymorphisms and toxicities after autologous stem-cell transplantation (ASCT) in adult patients with lymphoma or myeloma from 2015 to 2021 in two Brazilian transplant centers. All patients with available DNA to study genetic polymorphisms were included. In this analysis we evaluate the association between GATA polymorphism and self-declared color in this cohort. Results: A total of 217 patients were included in this analysis. Median age at transplantation was 56 years (21-79) and 130 patients (59.9%) were male. Most patients were self-declared white (n=175, 80.6%) and the most common genotype was GATA67T/T (wild type/wild type) (n=142, 65.4%). Among the self-declared white patients, 73.1% were genotyped as GATA67T/T and 4.0% as GATA-67C/C, while among the non-white patients 21.4% were genotyped as GATA-67C/C (p&lt;.001). The allele FY*B(-67T&gt;C) frequency was 0.22 in the whole population; it was identified in 26.9% of the self-declared white patients and in 66.6% of the non-white (p&lt;.001). Twelve-month overall survival was 86.6% (95% CI 79.9 - 91.2%), with no difference according to self-declared race (86.8% vs 85.5% for white and non-white patients, respectively, p=0.81) or the presence of the allele FY*B(-67T&gt;C) (85.2% vs 89.9% for non-mutated and mutated patients, respectively, p=0.27). Conclusion: GATA FY*B(-67T&gt;C) polymorphism is associated to self-declared race in Brazilian patients submitted to ASCT. Given the importance of correctly evaluating ancestry in genetic association studies in transplantation, GATA FY*B(-67T&gt;C) polymorphism can be used as a more accurate tool in populations with mixed ethnic/racial background.

Association of iron supplementation, HFE and AMPD1 polymorphisms and biochemical iron metabolism parameters in the performance of a men’s World Tour cycling team: A pilot study

BackgroundNutritional strategies with iron supplementation have been shown to be effective in preventing the decline of blood biochemical parameters and sports performance. The aim of the study was to describe biochemical iron metabolism parameters in association with iron supplementation and HFE and AMPD1 polymorphisms in a Union Cycliste Internationale (UCI) World Tour cycling team to evaluate performance during a whole season MethodsTwenty-eight professional men cyclists took part in this longitudinal observational pilot study. AMPD1 c.34 C>T (rs17602729) and HFE c.187 C>G (rs1799945) polymorphisms were genotyped using Single Nucleotide Primer Extension (SNPE). All the professional cyclists took oral iron supplementation throughout the season. Four complete blood analyses were carried out corresponding to UCI controls in January (1st), April (2nd), June (3rd) and October (4th). Data on participation in three-week Grand Tours, kms of competition and wins were analyzed. Results: In performance, especially in wins, there was a significant effect in HFE on biochemical hemoglobin (F = 4.255; p = 0.021) and biochemical hematocrit (F = 5.335; p = 0.009) and a hematocrit biochemical × genotype interaction (F = 3.418; p = 0.041), with higher values in professional cyclist with GC genotype. In AMPD1 there were significant effects in the biochemical iron x genotype interaction in three-week Grand Tours (F = 3.874; p = 0.029) and wins (F = 3.930; p = 0.028) ConclusionsBlood biochemical iron metabolism parameters could be related to performance in the season due to increasing hemoglobin and hematocrit concentration under iron supplementation, associated with winning in the professional cyclists with GC genotype of the HFE polymorphism.

Polymorphism of Transforming Growth Factor TGFB and Its Receptors TGFBRI, TGFBRII, TGFBRIIII Genes in Western Siberia Patients with Open-Angle Glaucoma.

Polymorphism of genes of transforming growth factor TGFB and its receptors (TGFBRI, TGFBRII, and TGFBRIIII) in patients with primary open-angle glaucoma was analyzed. The frequency of the TGFBRII CC genotype in patients is increased relative to the control group (OR=6.10, p=0.0028). Heterozygosity in this polymorphic position is reduced (OR=0.18, p=0.0052). As the effects of TGF-β is mediated through its receptors, we analyzed complex of polymorphic variants of the studied loci in the genome of patients. Two protective complexes consisting only of receptor genes were identified: TGFBRI TT:TGFBRII CG (OR=0.10, p=0.02) and TGFBRII CG:TGFBRIII CG (OR=0.09, p=0.01). The study showed an association of TGFBRII polymorphism with primary open-angle glaucoma and the need to study functionally related genes in the development of the disease, which should contribute to its early diagnosis and prevention.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment

BackgroundStudies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated.ObjectiveThis study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients.MethodsWe retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL).ResultsOur study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21–0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20–0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25–0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11–4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03–4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15–0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02).ConclusionWe found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Association of Cannabinoid-receptor 1 gene with Chronic Polysubstance Use among Nigerian Male Commercial Motor Vehicle drivers

The aim of the study was to evaluate the prevalence of psychoactive substance abuse and association of single nucleotide polymorphisms in Cannabinoid-Receptor 1 (CNR1) gene with chronic polysubstance use among the Nigerian male commercial vehicle drivers selected from the three major ethnic groups in Nigeria. A-10-Panel Generic Multi Drug Urine Dip Card Test Kit was used in the study and four SNPs (rs2023239, rs806378, rs806379 and rs806381)in CNR1 were genotyped in 60 subjects (20 drivers from each ethnic group) by using Sequenom MassARRAY Genotyping System. The four target SNPs revealed the following genotypes namely rs2023239: CC (20%), CT (40%), TT (40%); rs806378: CC (100%); rs806379: AA (20%), AT (50%), TT (30%); rs806381: AA (50%), GA (50%) in cases among the Hausa drivers. However, among the Igbo drivers, the four target SNPs showed the following genotypes namely rs2023239: CC (20%), CT (40%), TT (40%); rs806378: CC (80%) CT (20%); rs806379: AA (10%), AT (50%), TT (40%) and rs806381: AA (30%), GA (70%) in cases. Additionally, the target SNPs also revealed the following genotypes namely rs2023239: CC (30%), CT (30%), TT (40%); rs806378: CC (90%), CT (10%); rs806379: AA (10%), AT (60%), TT (30%) and rs806381: AA (70%), GA (20%), GG (10%) in cases among the Yoruba drivers. The SNPs rs2023239, rs806378 and rs806381 were significantly linked with polysubstance and chronic cannabis use in the sample population (Hausa, Igbo and Yoruba) (p˂0.05). The SNP rs806379 associated significantly with polysubstance and chronic cannabis use in the Igbo drivers only (p˂0.05). Conclusively, this study provides probably the first data on the association of CNR1genetic polymorphism with chronic polysubstance use among Nigerian male commercial motor vehicle drivers.

Association of Renin-Angiotensin Pathway Gene Polymorphisms with COVID-19 Susceptibility and Severity in Moroccans: A Case-Control Study.

Infection by the recent SARS-CoV-2 virus causes the COVID-19 disease with variable clinical manifestations ranging from asymptomatic or mild respiratory symptoms to severe respiratory distress and multiorgan failure. The renin-angiotensin system, responsible for maintaining homeostasis and governing several critical processes, has been considered the main system involved in the pathogenesis and progression of COVID-19. Here, we aimed to assess the possible association between variants in the RAS-related genes and COVID-19 susceptibility and severity in a sample of the Moroccan population. A total of 325 individuals were recruited in this study, with 102 outpatients, 105 hospitalized patients, and 118 healthy controls negative for SARS-CoV-2 infection, and subjected to NGS gene panel sequencing containing eleven RAS pathway genes. A total of 65 functional variants were identified, including 63 missenses, 1 splice, and 1 INDEL. Most of them were rare, with 47 (72%) found in a single individual. According to the common disease/common variant hypothesis, five common candidate variants with MAF > 10% were identified (ACE2 rs2285666, TMPRSS2 rs12329760, AGT rs699 genes, ACE rs4341, and ACE rs4343). Statistical analysis showed that the ACE rs4343 AA genotype was associated with a 2.5-fold increased risk of severe COVID-19 (p = 0.026), and the T genotype of the ACE2 rs2285666 variant showed a borderline association with susceptibility to SARS-CoV-2 in males (p = 0.097). In conclusion, our results showed that the RAS pathway genes are highly conserved among Moroccans, and most of the identified variants are rare. Among the common variants, the ACE rs4343 polymorphism would lead to a genetic predisposition for severe COVID-19.

Genetic association of the xenobiotic biotransformation system with the risk of death of the gestational sac in primigravida women living in an industrial city

Introduction. Every second conception in the population ends in failure, in 20% of the cases the cause is a non-developing pregnancy. In the overall structure of early reproductive losses, missed miscarriage accounts for 80%. The development of this pathology is influenced by both endogenous and exogenous factors. Exogenous factors with a teratogenic effect lead to the occurrence of mutations and the formation of an abnormal embryo, which is poorly predicted. The peculiarities of the biotransformation system of xenobiotics of the maternal organism directly affect the severity of the impact of these factors on the embryo. Materials and methods. A survey of eighty six young primigravida women living in Novokuznetsk was conducted. 33 of them were diagnosed with the gestational sac death, 53 women had a standard developed pregnancy. Variants of the GSTM1 and GSTT1 genes of the second phase of the xenobiotic biotransformation system were determined in these groups by polymerase chain reaction. Results. Novokuznetsk, a city with a critically high level of environmental pollution, has recorded a 20–fold increase in the number of missed miscarriages over the past 25 years. A statistically reliable association of deletion polymorphisms of the genes of the second phase of the xenobiotic biotransformation system with the death of the gestational sac - GSTM1 (χ2 – 5.37; OR – 3.18) and GSTT1 (χ2 – 10.85; OR – 16.64) was revealed, while the normal alleles were associated with a successful outcome of pregnancy - GSTM1 (χ2 – 5.37; OR – 0.13) and GSTT1 (χ2 – 10.85; OR – 0.06). Limitations. The study was of a pilot nature, so it is advisable to increase the sample in the future. Conclusion. The dependence between the activity of enzymes of the second phase of the xenobiotic biotransformation system and the increased risk of miscarriage of the first pregnancy in young women living in the conditions of ecological distress was revealed. The results of the study make it possible to predict possible pregnancy complications and elaborate algorithms for full-fledged pregravid preparation.

GOAT rs10096097 and CREB1 rs6740584 single nucleotide polymorphisms are associated with type 2 diabetes mellitus in Egyptians.

Diabetes mellitus (DM) is a chronic disorder that affects nearly half a billion people around the world and causes millions of deaths annually. Treatment of diabetes or related complications represents an economic burden not only for developing countries but also for the developed ones. Hence, new efficient therapeutic and preventive strategies and screening tools are necessary. The current work aimed to assess the potential association of single nucleotide polymorphisms (SNPs) in ghrelin O-acyltransferase (GOAT) rs10096097, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) rs6740584, and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) rs62521874 genes with type 2 DM susceptibility in Egyptians. A total of 96 patients with type 2 DM along with 72 healthy individuals participated in this study. Genotyping was executed via real-time polymerase chain reaction (PCR), and the serum protein levels of GOAT, CREB, and MafA were measured by enzyme-linked immunosorbent assay (ELISA). Genotyping revealed a significant association of GOAT rs10096097 and CREB1 rs6740584 SNPs with type 2 diabetes risk, with significantly higher GOAT rs10096097 G allele and CREB1 rs6740584 T allele frequencies in diabetic patients than in controls. However, insignificant association was identified between the MafA rs62521874 SNP and diabetes in the examined sample of the Egyptian residents. Serum GOAT, CREB1, and MafA protein levels did not vary significantly between diabetic and control individuals. Yet, significant variation in serum GOAT and CREB1 levels was detected between CREB1 rs6740584 genotypes within the diabetic group, with CT and TT genotype carriers showing higher levels than AA genotype patients. GOAT rs10096097 and CREB1 rs6740584, but not MafA rs62521874, SNPs are associated with type 2 diabetes risk in the studied Egyptians.

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21

BackgroundSingle nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear.MethodsA case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC.ResultsTCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells.ConclusionOur findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

Association of MMP-2 gene polymorphisms with diabetic retinopathy in tunisian population

Association of MMP-2 gene polymorphisms with diabetic retinopathy in tunisian population