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: 2.02). 12/2011; 39(4):5025-31. DOI: 10.1007/s11033-011-1299-8
Source: PubMed


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.

Download full-text


Available from: Ratika Samtani
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Chronic metabolic disorders such as cardiovascular disease and diabetes have become an emerging public health problem in India, in both rural and urban settings. Genetic markers like MTHFR, FV, ACE and APOE are important candidates involved in the development of these disorders. Aim: The present study aims to understand the distribution of allele frequencies of the SNPs in the above-mentioned genes in Manipuri Muslims, an endogamous religious community constituting ~8% of the Manipur population. Sample and methods: Blood samples were collected from 107 unrelated healthy individuals. Genotyping were done by PCR (for ACE I/D and MTHFR A1298C) followed by restriction digestion (for MTHFR C677T, FV G1691A and APOE). Results and discussion: All four SNPs, with the exception of FVL, were found to be polymorphic, with allele frequencies of 15.1%, 17%, 36.1% and 7.7% for MTHFR 677T, MTHFR 1298C, ACE D and APOE E4, respectively. The D allele of ACE I/D polymorphism was found to be significantly higher among males and also among the young age group compared with females and the old age groups, respectively. This study has highlighted the necessity of looking at the clinical implications of these SNPs in future studies of Manipuri Muslims.
    No preview · Article · Oct 2012 · Annals of Human Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Methylenetetrahydrofolate reductase () C677T, A1298C and methionine synthase reductase () A66G polymorphisms are important genetic determinants for homocysteine (Hcy) levels, and are associated with several disorders. These polymorphisms are heterogeneously distributed worldwide. Our objective was to explore the geographical distributions of these polymorphisms in China. METHODOLOGIES: 15357 healthy adults were recruited from 10 regions. Buccal samples were collected and genomic DNA was isolated. Genotyping was performed using the fluorogenic 5'-nuclease assay. The prevalence of the three polymorphisms among different populations from China varied significantly and showed apparent geographical gradients. For C677T, the frequencies of the 677T allele and the 677TT genotype were significantly higher among northern populations and ranged from the lowest values (24.0% and 6.4%, respectively) in Hainan (southern) to the highest values (63.1% and 40.8%, respectively) in Shandong (northern). For A1298C, the 1298C allele and the 1298CC genotype frequencies were significantly higher among southern populations and increased from low values (13.1% and 1.4%, respectively) in Shandong to high values (25.7% and 6.7%, respectively) in Hainan. For A66G, the 66G allele and the 66GG genotype frequencies increased from lower values (23.7% and 5.4%, respectively) in Shandong to higher values (29.2% and 8.6%, respectively) in Hainan. The overall frequency of the 677T allele, 677TT genotype, 1298C allele, 1298CC genotype, 66G allele and 66GG genotype in the Chinese Han population was 45.2%, 23.2%, 18.6%, 3.9%, 25.7%, and 6.6%, respectively. No gender differences were found in the prevalence of both the C677T and A66G polymorphisms. This study indicates that there are marked geographical variations in the prevalence of the three polymorphisms among Chinese Han populations. Our baseline data may be useful for future researches in related fields.
    Full-text · Article · Mar 2013 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Surnames have been used for studying population structure in different parts of the globe. The present study is aimed at indirectly estimating the degree of inbreeding from surnames and understanding the influences of the clan-like structure on mate selection among Manipuri Muslims. The proportion of isonymy I was found to be 0.0144. The non-random and random components were -0.0226 and 0.0239, respectively. The total inbreeding coefficient was estimated to be 0.0018. The scores of random pairs (RP) and random repeated pairs (RPr) were 0.026 and 0.010, respectively. The score of RP was higher than the RPr which gives a ratio of 0.38, indicating that Manipuri Muslims have a tendency of acquiring mates from within a given set of surnames while not in favour of isonymy. To conclude, surname/clan is a criterion for mate selection for various reasons among this population.
    No preview · Article · Apr 2013 · Homo: internationale Zeitschrift fur die vergleichende Forschung am Menschen
Show more