29. No association between MTHFR C677T polymorphism and congenital heart disease in Saudi Arabian population

Congenital heart diseases (CHD) are the most common birth defects in the world. It is a major cause of childhood mortality and morbidity worldwide with about 7 per 1000 live birth. Studies suggest that Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD), but the evidence remains inconclusive. The aim of this study is to determine whether this association exists in the Saudi Arabian population.MethodDNA sequencing was used to detect genotype MTHFR C677T in 75 CHD patients and 100 ethnically similar controls. The type of cardiac defect was diagnosed by cardiovascular specialist and confirmed by echocardiographic.ResultsThe distribution of the MTHFR 677C >T SNP genotypes and alleles in both CHD and control groups were 70.0% CC, 26.0% CT, 4.0% TT in cases and 70.8% CC, 25.4% CT, 3.8% TT in controls. The T allele frequency was 17.0% in cases and 16.5% in controls. The difference between genotypes and alleles was not statistically significant between controls and the CHD groups.ConclusionWe did not find sufficient evidence for an association between MTHFR C677T genotype and congenital heart disease in Saudi Arabian population. We agree that the sample size is a limitation to our above conclusions

Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation

Our understanding of the genetics of skin pigmentation has been largely skewed towards populations of European ancestry, imparting less attention to South Asian populations, who behold huge pigmentation diversity. Here, we investigate skin pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic Plain of the Indian subcontinent. Our data confirm the association of rs1426654 with skin pigmentation among South Asians, consistent with previous studies, and also show association for rs2470102 single nucleotide polymorphism. Our haplotype analyses further help us delineate the haplotype distribution across social categories and skin color. Taken together, our findings suggest that the social structure defined by the caste system in India has a profound influence on the skin pigmentation patterns of the subcontinent. In particular, social category and associated single nucleotide polymorphisms explain about 32% and 6.4%, respectively, of the total phenotypic variance. Phylogeography of the associated single nucleotide polymorphisms studied across 52 diverse populations of the Indian subcontinent shows wide presence of the derived alleles, although their frequencies vary across populations. Our results show that both polymorphisms (rs1426654 and rs2470102) play an important role in the skin pigmentation diversity of South Asians

The polymorphism at the microRNA-155 binding site in AGTR1 gene is not significantly associated with rheumatic heart disease in Saudi Arabia population

Rheumatic heart disease (RHD) remains a major cause of cardiovascular diseases and the most devastating effects are on children and young adults. RHD is caused due to the interaction between microbial, environmental, immunologic, and genetic factors. The renin-angiotensin aldosterone system (RAAS) has been strongly implicated as the susceptibility pathway in the pathogenesis of cardiovascular disease. The present study investigated the modulating effect of Angiotensin II type 1 receptor (AGTR1) 1166A>C polymorphism on the RHD and its clinical features in Saudi Arabia. AGTR1 1166A>C polymorphism was genotyped in 96 echocardiographically confirmed RHD patients and 142 ethnically matched controls by TaqMan allelic discrimination method. Genotype distribution of the AGTR1 1166A>C polymorphism was not significantly different between RHD and control groups. Further, AGTR1 1166A>C genotypes are not associated with the clinical features of RHD. These data support that there was no evidence for an association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. To our knowledge, this is the first study that has investigated the possible association between AGTR1 1166A>C polymorphism and susceptibility to RHD and its clinical features. Even though AGTR1 gene is 1166A>C (rs5186) was reported to be associated with hypertension, left ventricular hypertrophy and coronary heart disease. Present study did not find any association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. Further studies are needed to confirm our findings

SRD5A2 gene polymorphisms and the risk of benign prostatic hyperplasia but not prostate cancer

Background: Testosterone, a primary androgen in males, is converted into its most active form,Dihydrotestosterone (DHT), by 5α-reductase type 2 (encoded by the SRD5A2 gene) in the prostate. DHT is necessary for prostatic growth and has five times higher binding affinity than testosterone for androgen receptors. We hypothesized that polymorphic variations in the SRD5A2 gene may affect the risk of benign prostatichyperplasia and prostate cancer. Materials and Methods: We analyzed SRD5A2 gene polymorphisms in 217 BPH patients, 192 PCa cases and 171 controls. Genotyping was undertaken using direct DNA sequencing. Genotype data were compared between cases and controls using a Chi square statistical tool. Results: We found that the A49T locus was monomorphic with ‘AA’ genotype in all subjects. At V89L locus, the presence of ‘VV’ showed a marginally significant correlation with increased BPH risk (p = 0.047). At the (TA)n locus, longer TA repeats were found to be protective against BPH (p = 0.003). However, neither of these polymoprhisms correlated with the risk of PCa. Conclusions: We conclude that A49T is monomorphic in the study population, VV marginally correlates with BPH risk and longer (TA) n repeats are protective against BPH. None of these polymorphisms affect the risk of PCa

Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis.

BACKGROUND:Optimum efficiency of the folate pathway is considered essential for adequate ovarian function. 677 C>T substitution in the 5, 10-methylene tertrahydrofolatereductase (MTHFR) gene compromises activity of the MTHFR enzyme by about 50%. The significance of correlation between 677C>T substitution and PCOS remains dubious due to the low power of published studies. METHODS AND RESULTS:We analyzed MTHFR 677 C>T site in ethnically two different PCOS case-control groups (total 261 cases and 256 controls) from India. The data analysis revealed a lack of association between this polymorphism and PCOS [OR = 1.11 (95%CI = 0.71-1.72), P = 0.66]. Group-wise analysis on the basis of ethnicity also revealed no association in any of the ethnic groups [Indo-Europeans, P = 1; Dravidians, P = 0.70]. Homocysteine levels did not differ significantly between cases (15.51 μmol/L, SD = 2.89) and controls (15.89 μmol/L, SD = 2.23). We also undertook a meta-analysis on 960 cases and 1028 controls, which suggested a significant association of the substitution with PCOS in the dominant model of analysis (OR = 1.47 (95%CI = 1.04-2.09), P = 0.032]. Trial sequential analysis corroborated findings of the traditional meta-analysis. However, we found that the conclusions of meta-analysis were strongly influenced by studies that deviated from the Hardy Weinberg equilibrium. A careful investigation of each study and a trial sequential analysis suggested that 677 C>T substitution holds no clinical significance in PCOS in most of the populations. CONCLUSION:In conclusion, MTHFR 677 C>T polymorphism does not affect PCOS risk in India. The association seen in the meta-analysis is due to an outlier study and studies showing deviation from the Hardy Weinberg equilibrium

Distribution and comparison of various clinical parameters between hyper- and normo-androgenic groups.

<p>Distribution and comparison of various clinical parameters between hyper- and normo-androgenic groups.</p

Results of meta-analysis (random effects model) using different analysis models.

<p>Results of meta-analysis (random effects model) using different analysis models.</p

Sensitivity analysis excluding the studies not fitting the Hardy Weinberg equilibrium.

<p>Sensitivity analysis excluding the studies not fitting the Hardy Weinberg equilibrium.</p

Meta-analysis.

<p>Forest plot showing the odds ratio, p value and direction of association between MTHFR 677 C>T polymorphism and PCOS. The Z value shows the degree and direction of the relationship, whereas the P value shows significance of the relationship. The horizontal bar shows the range of OR with a square in the centre, size of the latter is directly proportional to the weight given to each study. The direction of projection of the horizontal bar shows the direction of association.</p