Genotype Frequencies Research Articles

Effects of MTHFR C677T polymorphism on homocysteine and vitamin D in women with polycystic ovary syndrome

ObjectivesTo evaluate the correlation between serum vitamin D, homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism in women with polycystic ovary syndrome (PCOS).Study designWe retrospectively compared the serum homocysteine and vitamin D levels and the MTHFR C677T polymorphism in 104 PCOS patients and 104 controls. Parameters related to PCOS were statistically analysed. ResultsComparative analysis revealed that women with PCOS had significantly greater serum homocysteine levels (P = 0.002) and lower vitamin D concentrations (P = 0.040) than controls. The distribution frequency of the MTHFR C677T genotype did not significantly differ between the PCOS group and the control group. (P > 0.05). In the PCOS group, the serum level of homocysteine in the TT group was significantly greater than that in the CT (P = 0.003) and CC (P = 0.002) groups and the level of vitamin D in the TT group was significantly less than that in the CC (P < 0.001) and CT (P = 0.172) groups. The results were similar when the PCOS and control groups were divided according to whether they had insulin resistance. Vitamin D levels were significantly negatively correlated with homocysteine levels in all PCOS patients (r = −0.281, P = 0.004), similarly, vitamin D levels were negatively correlated with homocysteine levels in the CC, CT and TT of PCOS patients. According to multivariate analysis, vitamin D concentration was an independent risk factor for hyperhomocysteinaemia (adjusted OR 1.372, 95 % CI: 1.100–1.712). ConclusionsNo significant differences were found in the distributions of MTHFR C677T genotypes between the PCOS and control groups but these genotypes affected the patients’ serum homocysteine and vitamin D concentrations. Women with the TT genotype have significantly lower vitamin D levels and higher homocysteine levels than women with the CC and CT genotypes. However, because of the limitations of this investigation, large-sample, high-quality prospective studies are needed to further verify these results in the future.

The role of the CNTNAP2 gene in the development of autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetic and environmental factors interact in its development. Research suggests that the contactin associated protein 2 (CNTNAP2) gene may play a role in ASD pathophysiology, yet more studies involving human participants and animal models of autism are needed. One such model may be the use of prenatal valproic acid (VPA) model to induce autism-like behaviors in offspring rats. The aim of this study was twofold: (1) to examine the association of the CNTNAP2 gene rs2710102 variant with ASD in children; and (2) to examine the effect of prenatal exposure to VPA on Cntnap2 gene expression in the rat brain. The study included 167 children of European ancestry—81 diagnosed with ASD (20 girls, 61 boys; age 4.9 ± 1.4 years) and 86 controls (44 girls, 42 boys; 5.1 ± 1.2 years). In vivo experiments were conducted in 80 rats (40 with the VPA model of autism), with Cntnap2 gene expression analysis in the amygdala, hippocampus, prefrontal cortex, and cerebellum. Results demonstrated that the frequency of the CNTNAP2 gene rs2710102 GG genotype was significantly higher in children with ASD when compared with controls (33.3 vs 19.8%; OR=2.03, 95%CI [1.004, 4.102], p = 0.035), although, potentially due to bias in cohort selection, in the ASD children this polymorphism did not meet Hardy-Weinberg expectations (χ2 =5.40, p = 0.02). In addition, Cntnap2 gene expression was significantly lower (p < 0.01) in the amygdala and hippocampus of VPA rats when compared with controls, regardless of sex. These results support previous research and provide evidence for the CNTNAP2 gene as a risk factor for ASD.

Prevalence of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans: implications for a North African Neanderthal connection

The clinical presentation of COVID-19 shows high variability among individuals, which is partly due to genetic factors. The OAS1/2/3 cluster has been found to be strongly associated with COVID-19 severity. We examined this locus in the Moroccan population for the occurrence of the critical variant rs10774671 and its respective haplotype blocks. The frequency of single-nucleotide polymorphisms (SNPs) in the cluster of OAS immunity genes in 157 unrelated individuals of Moroccan origin was determined using an in-house exome database. OAS1 exon 6 of 71 SARS-CoV-2-positive individuals with asymptomatic/mild disease and 74 with moderate/severe disease was sequenced by the Sanger method. The genotypic, allelic, and haplotype frequencies of three SNPs were compared between these two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. The prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was found to be 40.4%, which is similar to that found in Europeans. However, it was found equally in both the Neanderthal GGG haplotype and the African GAC haplotype, with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008, respectively). Surprisingly, in men with the Berber-specific uniparental markers, the African haplotype was absent, while the prevalence of the Neanderthal haplotype was similar to that in Europeans. The protective rs10774671-G allele of OAS1 was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as a stepping-stone for the passage of hominids to other continents.

Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

Fatty acid composition of erythrocyte membranes in carries of rs174544 polymorphism of FADS1 gene and rs174583 polymorphism of FADS2 gene from central region of the Russian Federation before and after supplementation of their diet with ω-3 PUFAs

Numerous publications have demonstrated that polymorphisms in FADS1 and FADS2 gene cluster influence the levels of long chain polyunsaturated fatty acids (LC PUFAs) synthesized in the body from essential precursors. They can be consumed through the diet as well. These LC PUFAs perform important plastic and regulatory functions in the body. The associations between the polymorphisms of FADS genes and the fatty acid (FA) composition of the body with some inflammatory and chronic diseases were shown. To date, very few studies in the Russian Federation researched the distribution of polymorphic variants in FADS1 and FADS2 genes and no studies examined the effects of these polymorphisms on the level of FAs in tissues.So, the purpose of this paper was to study the frequency of genotypes and alleles of the rs174544 polymorphism of the FADS1 gene and the rs174583 polymorphism of the FADS2 gene and their influence on the FA composition of erythrocyte membranes in residents of the Central region of the Russian Federation (RF). Additionally, the effect of ω-3 PUFAs fortified food products on this composition was examined. MethodsThe study included 70 volunteers aged 23–69 years from Moscow region who provided informed consent. They were genotyped for rs174544 polymorphism of FADS1 gene and rs174583 polymorphism of FADS2 gene by real-time PCR. The participants of the study consumed fruit or vegetable smoothies enriched with either vegetable (chia seeds flour) or animal (fish oil flour) sources of ω-3 PUFAs for 1 month. The fatty acid composition of erythrocyte membranes in some of the volunteers was analysed using gas-chromatography before and after fortification of their diet with ω-3 PUFAs. Statistical analysis was performed using SPSS 23. ResultsThe frequency of genotypes and alleles of polymorphisms studied were similar to those published for the European region. For rs174544, the genotype frequencies were CC (61%), CA (29%), and AA (10%), frequency of allele A was 24%. For rs174583, the genotype frequencies were CC (51%), CT (39%), and TT (10%), frequency of allele T was 29%. Carriers of minor alleles of both polymorphisms studied had significantly higher levels of ω-6 and ω-3 LC PUFAs in erythrocyte membranes compared to those carrying other genotypes. This differs from the results of other studies where carriers of minor alleles as were shown to be slow converters of precursors to LC PUFAs. The reason of the discrepancy was most likely associated with the obesity and dietary preferences of our study participants who carry the minor alleles. Over the period of one-month consumption of food sources providing an additional intake of either 2 g/day ω-3 PUFAs from fish oil or 6.5 g/day of ω-3 PUFAs from chia seed flour markedly reduced the incorporation of ω-6 PUFAs into erythrocyte membranes in carriers of minor alleles. Additionally, there was an increase in the content of saturated palmitic acid in the membranes that noticeably changed the fatty acid composition of erythrocyte membranes. ConclusionOur results confirm the observation that blood fatty acid composition related to polymorphisms of FADS gene is highly influenced by BMI. The incorporation of ω-6 PUFAs into erythrocyte membranes decreases when the diet is fortified with ω-3 PUFAs. This decrease can help reduce the formation of pro-inflammatory eicosanoids and the risk of various inflammatory and chronic diseases, especially in carriers of minor alleles of the genetic polymorphisms studied.

Association of KLOTHO gene variants with metabolic and renal function parameters in Mexican patients living with type 2 diabetes.

Type 2 diabetes (T2D) and high blood pressure are the main causes of chronic kidney disease (CKD) in adulthood. Both metabolic and oxidative stresses driven by hyperglycemia as well as genetic factors have been suggested as pathogenic causes of renal failure. Some single nucleotide variants (SNVs) on gene coding KLOTHO (KL) have been implicated in several clinical scenarios including hypertension, diabetes, and cardiovascular disease. The aim of this study was to analyze the association of rs1207568 (-395G > A), rs953614 (+ 1062T > G) and rs564481 (+ 1818C > T) SNVs with metabolic and renal function parameters in Mexican patients living with type 2 diabetes. A cross-sectional study was conducted in 637 Mexican patients with T2D, and/or hypertension without previous diagnosis of CKD. Anthropometric, metabolic, and renal function parameters were determined. Patients were genotyped for rs1207568, rs953614 and rs564481 SNVs and associations under a dominant genetic model were analyzed by logistic regression. For rs9536314, G-allele showed to be protective for hypo-HDL-C, albuminuria, and CKD. Carriers of minor allele of rs564481 had low odds for high glucose levels. No differences in genotype nor allele frequencies between the patients and the reference population were observed. In Mexican patients living with type 2 diabetes, KL variant rs9536314 was found associated with low odds of hypo-HDL cholesterol, albuminuria and presence of CKD. Meanwhile the consensus of soluble KLOTHO measurement is reached, genetic variants in the KL gene could be considered as genetic markers for CKD susceptibility in patients at high-risk of vascular complications.

Screening of single nucleotide polymorphism in matrix metalloproteinase-2 (MMP2) and tetraspanin CD63 genes in Chlamydia trachomatis-infected tubal ectopic pregnancy patients.

Tubal ectopic pregnancy (EP) is a leading cause of maternal morbidity and mortality. Studies have suggested that infection-induced inflammatory responses are major risk factors for EP. The aim of the present study was to find an association between MMP2 and CD63 gene variants and risk of EP during Chlamydia trachomatis infection in an Indian population. Fallopian tube samples of 120 EP and 120 tubal ligation women were collected. C. trachomatis was detected by PCR. The genotyping of MMP2 (rs17859882 G/T, rs7201A/C) and CD63(rs2231464 C/T, rs376086542 A/G) gene variants was done by qualitative real-time PCR using allelic discrimination method (VIC- and FAM-labeled). The frequency of GG or GT genotype of MMP2 G/T polymorphism (rs17859882) was 66.6% in infected EP and 36.7% in uninfected EP and 22% in tubal ligation controls (P < 0.0001), while the frequency of AC or CC genotype of MMP2 A/C polymorphism (rs7201) was 66.6% in infected EP and 20.6% in uninfected EP and 13.5% in tubal ligation controls (P < 0.0001). The frequency of CT or TT genotype of CD63 C/T polymorphism (rs2231464) was 74% in infected EP and 21.8% in uninfected EP and 11.8% tubal ligation controls (P < 0.0001), while the frequency of AG or GG genotype of CD63 A/G polymorphism (rs376086542) was 48.1% in infected EP and 41.3% in uninfected EP and 18.6% tubal ligation controls (P < 0.0001). The present study revealed a strong association between the presence of gene variants MMP2 (rs17859882 G/T, rs7201A/C) and CD63 (rs2231464 C/T, rs376086542 A/G) and risk of tubal EP during C. trachomatis infection.

IL-10 and IL-1β Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults' Clinical Characteristics.

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarly, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Association of the IFNG +874T/A Polymorphism with Symptomatic COVID-19 Susceptibility.

Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.

APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin.

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52-15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.

A panel of tetranucleotide STR markers as an alternative approach to forensic DNA identification of wolf and dog.

Commercial panels of microsatellite (STR) loci are focused on the use of DNA of the domestic dog (Canis lupus familiaris) and are often inapplicable for genotyping the DNA of the gray wolf (Canis lupus lupus). We propose a CPlex test system, including one hexa- and 12 tetranucleotide autosomal STR loci, as well as two sex loci, that is equally efficient in DNA identification of biological samples of the wolf and the dog. Analysis of molecular variance between samples revealed significant differentiation values (FST = 0.0784, p < 0.001), which allows to use the panel to differentiate wolf and dog samples. Population subdivision coefficients (θ-values) were calculated for each of the 13 STR loci of the developed test system. It was shown that the values of the genotype frequency for dogs and wolves, without and with considering the θ-value, differ by three orders of magnitude (for dogs 8.9 × 10-16 and 2.1 × 10-14 and for wolves 1.9 × 10-15 and 4.5 × 10-14, respectively). The use of population subdivision coefficients will allow to identify the most reliable results of an expert identification study and the power of exclusion provided by the STR loci of the CPlex test system makes it possible to achieve a reliable level of evidence in forensic DNA analysis of both wolves and dogs. The test system has been validated for use in forensic identification of the dog and wolf based on biological traces found at crime scenes, as well as for individual identification and establishing biological relationship of animals of these species.

Frequencies of CYP2C19 and CYP2D6 gene variants in a German inpatient sample with mood and anxiety disorders

Objectives Previous results demonstrated that CYP2D6 and CYP2C19 gene variants affect serum concentrations of antidepressants. We implemented a PGx service determining gene variants in CYP2D6 and CYP2C19 in our clinical routine care and report on our first patient cohort. Methods We analysed CYP2D6 and CYP2C19 allele, genotype, and phenotype frequencies, and actionable pharmacogenetic variants in this German psychiatric inpatient cohort. Two-tailed z-test was used to investigate for differences in CYP2D6 and CYP2C19 phenotypes and actionable/non-actionable genetic variant frequencies between our cohort and reference cohorts. Results Out of the 154 patients included, 44.8% of patients were classified as CYP2D6 normal metabolizer, 38.3% as intermediate metabolizers, 8.4% as poor metabolizers, and 2.6% as ultrarapid metabolizers. As for CYP2C19, 40.9% of patients were classified as normal metabolizers, 19.5% as intermediate metabolizers, 2.6% as poor metabolizers, 31.2% as rapid metabolizers, and 5.8% as ultrarapid metabolizers. Approximately, 80% of patients had at least one actionable PGx variant. Conclusion There is a high prevalence of actionable PGx variants in psychiatric inpatients which may affect treatment response. Physicians should refer to PGx-informed dosing guidelines in carriers of these variants. Pre-emptive PGx testing in general may facilitate precision medicine also for other drugs metabolised by CYP2D6 and/or CYP2C19.

Association of common single-nucleotide polymorphism of HHEX with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that occurs as a result of insulin resistance and low insulin production. T2DM involves many organ systems that include macro-vascular and micro-vascular complications. Several genome-wide association studies (GWAS) and candidate gene studies have suggested a large number of single nucleotide polymorphisms (SNPs) on several genes such as HHEX that were associated with T2DM susceptibility. The current study aims to look at the relationship between the risk of T2DM and the HHEX gene variant rs7923837. In this case-control study genotyping of rs7923837 of the HHEX gene was performed using the PCR-RFLP and Sanger sequencing method. Frequencies of GG genotype of rs7923837 polymorphism of HHEX among subjects with and without diabetes mellitus were 33.77% and 25.47% respectively. Corresponding prevalence for the AG genotype was 51.08% and 64.15% among subjects with and without diabetes mellitus respectively. The differences were not statistically significant (p = 0.08). Our study revealed that polymorphisms rs7923837 of HHEX were not associated with T2DM. The online version contains supplementary material available at 10.1007/s40200-024-01407-5.

The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population.

Anti-E alloantibody is the most common and important red blood cell(RBC) alloantibody during pregnancy. The study aimed to determine the correlation between RhE alloimmunization and human leukocyte antigen (HLA)allele polymorphism, as well as haplotype diversity, among pregnant individuals in the Chinese Han population. All individuals included in our study were RhE-negative pregnant women of Chinese Han ethnicity, confirmed through serological testing. Pregnancy could be the only potential stimulating factor in RBC alloimmunization. Given the serological testing, the participants were divided into anti-E (responders) and non-anti-E-producing group (non-responders). The class I and II classical HLA genotyping were determined using next-generation sequencing, and the HLA genotype and haplotype frequencies were compared between the responders and non-responders. In total, 76 responders and 94 non-responders were enrolled in this study. Comparison results showed that all HLA class I alleles had no difference between the two groups. For HLA class II phenotypes, responders had higher frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02 and HLA-DQB1*03:03 phenotypes than non-responders, and the differences were statistically significant (pc < 0.05). In addition, the haplotype frequency of HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 in the RhE responders was significantly higher than in the non-responders (31.58% vs. 12.77%; odds ratio, 3.154; 95% confidence interval, 1.823-5.456; pc value, 1.25 × 10-3). Our findings indicated that HLA-DRB1*09:01, HLA-DQA1*03:02 and HLA-DQB1*03:03 might be susceptible alleles for RhE alloimmunization among Chinese Han pregnant females. These three susceptible alleles constituted the unique three-locus haplotype in the RhE responders and collaborated to RhE alloimmunization.

Gene Variants of the OAS/RNase L Pathway and Their Association with Severity of Symptoms and Outcome of SARS-CoV-2 Infection.

The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes. Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.

Analysis of Elimination Effects of Inbreeding on Genotype Frequency in Larval Stages of Chinese Shrimp.

Marine animals possess genomes of considerable complexity and heterozygosity. Their unique reproductive system, characterized by high fecundity and substantial early mortality rates, increases the risk of inbreeding, potentially leading to severe inbreeding depression during various larval developmental stages. In this study, we established a set of inbred families of Fenneropenaeus chinensis, with an inbreeding coefficient of 0.25, and investigated elimination patterns and the manifestations of inbreeding depression during major larval developmental stages. Reduced-representation genome sequencing was utilized to explore the genotype frequency characteristics across two typical elimination stages. The results revealed notable mortality in hatching and metamorphosis into mysis and post-larvae stages. Inbreeding depression was also evident during these developmental stages, with depression rates of 24.36%, 29.23%, and 45.28%. Segregation analysis of SNPs indicated an important role of gametic selection before hatching, accounting for 45.95% of deviation in the zoea stage. During the zygotic selection phase of larval development, homozygote deficiency and heterozygote excess were the main selection types. Summation of the two types explained 82.31% and 89.91% of zygotic selection in the mysis and post-larvae stage, respectively. The overall distortion ratio decreased from 22.37% to 12.86% in the late developmental stage. A total of 783 loci were identified through selective sweep analysis. We also found the types of distortion at the same locus could change after the post-larvae stage. The predominant shifts included a transition of gametic selection toward normal segregation and other forms of distortion to heterozygous excess. This may be attributed to high-intensity selection on deleterious alleles and genetic hitchhiking effects. Following larval elimination, a greater proportion of heterozygous individuals were preserved. We detected an increase in genetic diversity parameters such as expected heterozygosity, observed heterozygosity, and polymorphic information content in the post-larvae stage. These findings suggest the presence of numerous recessive deleterious alleles and their linkage and suggest a major role of the partial dominance hypothesis. The results provide valuable insights into the mechanisms of inbreeding depression in marine animals and offer guidance for formulating breeding strategies in shrimp populations.

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.

Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between IL-27 and IL-35 gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the IL-27 gene (rs181206, rs153109, and rs17855750) and the IL-35 gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the IL-27 and IL-35 genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the IL-35 gene was significantly decreased in patients with PTB when compared to controls (p = 0.036). Stratified analysis suggested that the frequency of the IL-27 rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the IL-35 rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The IL-35 rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, IL-35 gene variation might contribute to a protective role on the susceptibility to PTB, and IL-27 and IL-35 gene polymorphisms were associated with several clinical manifestations of patients with PTB.

Genetic insights into Cyphocharax magdalenae (Characiformes: Curimatidae): Microsatellite loci development and population analysis in the Cauca River, Colombia.

Cyphocharax magdalenae, a Colombian freshwater fish species, plays a vital role in nutrients distribution and serves as a significant food source for other fish species and local fishing communities. Considered a short-distance migratory species, C. magdalenae populations face substantial extinction risk due to human activities impacting their habitats. To address the lack of knowledge on genetic diversity and population structure, this study used next-generation sequencing technology to develop species-specific microsatellite loci and conducted a population genetics analysis of C. magdalenae in the middle and lower sections of the Cauca River, Colombia. Out of 30 pairs of microsatellite primers evaluated in 324 individuals, 14 loci were found to be polymorphic, at linkage equilibrium and, in at least one population, their genotypic frequencies were in Hardy-Weinberg equilibrium. Results showed high genetic diversity levels compared to other neotropical Characiformes, with inbreeding coefficients similar to those reported for phylogenetically related species. Moreover, C. magdalenae exhibits seasonal population structure (rainy-dry) consisting of two genetic stocks showing bottleneck signals and high effective population sizes. This information is essential for understanding the current species genetics and developing future management programs for this fishery resource.

An artificial-restriction fragment length polymorphism (A-RFLP) method for genotyping intronic SNP rs7587633 C/T of ATG16L1

SNPs could either cause a disorder or directly alter the efficacy of a particular treatment and act as biological markers. The SNP rs7587633 C/T present in the intronic region of the ATG16L1 gene has been studied for its role in psoriasis vulgaris and Palmoplantar pustulosis. To genotype rs7587633 C/T using PCR-RFLP no restriction site is present for any of the restriction enzymes at the SNP position. To develop an artificial-RFLP method for genotyping rs7587633 C/T, the forward primer was designed in such a way that it resulted in the creation of an EcoRI restriction site in the amplified product which could further be digested with EcoRI to find the genotype of the individual. The newly developed A-RFLP method was applied to genotype the SNP rs7587633 C/T in DNA samples of 100 healthy control individuals. The allelic and genotypic frequencies of the SNPs were 0.80(C), 0.20(T) and 65%(CC), 31%(CT) and 4%(TT), respectively. In conclusion, we developed an A-RFLP method to genotype the SNP rs7587633 C/T which is not present in any of the natural restriction sites and this method could be applied to genotype this SNP in various populations/diseases to find its role.

Prevalence of variants of the FAD-dependent amino oxidase gene in adolescents with internet addiction

The aim of the research was to study the prevalence of rs1137070 MAOA polymorphism in Tuvan, Khakass and Russian adolescents, as well as the degree of their Internet addiction, assessed on the Chen scale. Materials and methods. The study included 559 adolescents of the Angara-Yenisei macroregion (Tuvinians, Khakas, Russians). The type of Internet addiction was assessed on the Chen scale, polymorphism was detected using real-time PCR. Results. It was revealed that the frequency of the TT rs1137070 genotype of the MAOA associated with low activity of the MAOA enzyme is significantly higher in Tuvan adolescents compared to Russians (31.1% vs. 21.2%, p=0.020). Pathological Internet addiction is more often observed among Khakas compared to Russian adolescents (26.4% vs. 15.5%, p=0.028). Thus, it is shown that the presence of a tendency to Internet addiction is potentially observed in carriers of the allele variant T rs1137070 MAOA, and Tuvans and Khakas, like other Asian populations, are more susceptible to the development of pathological dependencies, relative to Russians.