Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups of India

Biochemical and Molecular Lab, Department of Anthropology, University of Delhi, Delhi, 110007, India.
Molecular Biology Reports (Impact Factor: 1.96). 12/2011; 39(4):5025-31. DOI: 10.1007/s11033-011-1299-8
Source: PubMed

ABSTRACT Elevated homocysteine is a risk factor for many complex disorders. The role of methylenetetrahydrofolate reductase (MTHFR) gene in methylation of homocysteine makes it one of the most important candidate genes for these disorders. Considering the heterogeneity in its distribution in world populations, we screened MTHFR C677T and A1298C single nucleotide polymorphisms in a total of 23 Indian caste, tribal and religious population groups from five geographical regions of India and belonging to four major linguistic groups. The frequencies of MTHFR 677T and 1298C alleles were found to be 10.08 and 20.66%, respectively. MTHFR homozygous genotype 677TT was absent in eight population groups and homozygous 1298CC was absent in two population groups. 677T allele was found to be highest among north Indian populations with Indo-European tongue and 1298C was high among Dravidian-speaking tribes of east India and south India. The less common mutant haplotype 677T-1298C was observed among seven population groups and overall the frequency of this haplotype was 0.008, which is similar to that of African populations. cis configuration of 677T and 1298C was 0.94%. However, we could not find any individual with four mutant alleles which supports the earlier observation that presence of more than two mutant alleles may decrease the viability of foetus and possibly be a selective disadvantage in the population.

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    ABSTRACT: Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r = 0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P = 0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid.
    01/2014; 2014:560183. DOI:10.1155/2014/560183
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    ABSTRACT: Methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism shows considerable heterogeneity in its distribution in humans worldwide. The current study was conducted to investigate whether this polymorphism exhibited adaptive developmental plasticity in the control of the TT-genotype frequency. We screened 1,818 South Indian subjects (895 males and 923 females) for MTHFR C677T polymorphism using PCR-restriction fragment length polymorphism approach. MTHFR 677T-allele frequency in males and females was 9.1 and 11.0 %, respectively. Compared to females, males had lower frequency of TT-genotype [odds ratio 0.31, 95 % confidence interval (CI) 0.08-1.01]. The frequency of MTHFR 677T-allele was highest in the age group of 20-40 years and it gradually decreased from 40-60 to 60-80 years (P trend <0.0001). MTHFR 677TT-genotype was associated with 7.02-folds (95 % CI: 2.12-25.63, P < 0.0001) cumulative risk for recurrent pregnancy loss (RPL), neural tube defects (NTDs) and deep vein thrombosis (DVT). Linear regression model suggested that male gender exhibited increased homocysteine levels by 9.35 μmol/L while each MTHFR 677T-allele contributed to 4.63 μmol/L increase in homocysteine. Plasma homocysteine showed inverse correlation with dietary folate (r = -0.17, P < 0.0001), B2 (r = -0.14, P < 0.0001) and B6 (r = -0.07, P = 0.03). Examination of the spontaneously aborted fetuses (n = 35) showed no significant association of fetal genotype on its in utero viability. From the current study, it was concluded that C677T seemed to have acquired adaptive developmental plasticity among South Indians due to environmental influences thus contributing to hyperhomocysteinemia and its associated complications such as RPL, NTDs, DVT, etc.
    Molecular Biology Reports 01/2014; 41(5). DOI:10.1007/s11033-014-3163-0 · 1.96 Impact Factor
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    ABSTRACT: Abstract Background: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been suggested to be positively associated with several disorders. Distribution of the mutant T-allele varies in ethnic and geographical populations of the world. Aim: The aim of the present study was to investigate the distribution of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in a transhumant (Gaddi) tribal population of Himachal Pradesh dwelling at high and middle altitude and exposed to strong ultraviolet radiation. Method and results: A total of 486 samples (141 males and 345 females) were randomly enrolled from the individuals aged 25-75 years who were unrelated up to first cousin. Among Gaddis, genotype frequencies of CC, CT and TT were 67.90%, 27.78% and 4.32%, respectively. Among males and females distribution of genotype frequencies also followed a similar trend. The studied population was in Hardy-Weinberg equilibrium (χ(2 )= 2.213, df = 1, p = 0.136). Frequency of mutant T-allele in the Gaddi population was found to be 0.183, which might be due to European ancestry, endogamous nature and selection.
    Annals of Human Biology 06/2014; 41(6):1-3. DOI:10.3109/03014460.2014.920917 · 1.15 Impact Factor


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