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Nutrigenomics and Molecular Nutrition

Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its modulation by vitamin B12 and folic acid in an Indian population

European Journal of Clinical Nutrition volume 66, pages 111–118 (2012)Cite this article

Abstract

Background/Objectives:

Unlike most Western populations, MTHFR 677T is a rare allele and a risk factor for a variety of disorders in India. What kind of nutritional (environmental) and/or genetic factors could contribute to the genetic risk is not known. To assess the incidence of hyperhomocysteinemia and its correlation with the polymorphism in homocysteine (Hcy)-pathway genes and associated cofactors in the native populations of eastern India.

Subjects/Methods:

Healthy population from four eastern states of India. Genotyping of SNPs, HPLC and chemiluminescence-based assay for homocysteine, vitamin B12 and folic acid.

Results:

Approximately 30% of the population has hyperhomocysteinemia (>15 μmol/lit; hypHcy) with varying frequencies in the four states from where samples were collected (n=1426). Polymorphisms of MTR and CBS do not affect hypHcy. 677T and 1298C alleles of MTHFR and G80 RFC-1 show association with hypHcy. In contrast, RFC-1 80AA is protective even in presence of 677T MTHFR. Addition of each mutant allele has an additive effect on Hcy level. Vitamin B12 (cofactor in methionine synthesis) clearly modulates the genotypic effect on Hcy level. Although frequency of individuals with low folic acid is ∼11, 49% of the population is vitamin B12 deficient (<220 pg/lit) and has a significant negative correlation with Hcy. Individuals with optimum vitamin B12 and folic acid generally have low Hcy, even in risk genotypes.

Conclusions:

One of the plausible reasons for susceptibility of individuals with MTHFR C677T in the studied population to various disorders is the high frequency of hyperhomocysteinemia and vitamin B12 deficiency in the ‘healthy population’. Apparently, supplementation of vitamin B12 to this health-impoverished community may help lessen the risk of several multifactorial disorders.

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Acknowledgements

We record our appreciation of the volunteers who made themselves available for the study, and the staff of the primary health centres of various districts for making it possible to reach the public at large. We are grateful to Dr Shantanu Sengupta, IGIB, Delhi and Dr CS Yajnik, KEM Hospital, Pune for helping us standarise the methodologies for homocysteine and micronutrients and performing initial measurements in their labs. We are indebted to Professor SK Singh, Institute of Medical Sciences, BHU for conducting Chemiluminiscence assay of vitamin B12 and folic acid. Financial support by the Department of Biotechnology, New Delhi, in the form of programme support (RR) and fellowship (KKS) is acknowledged.

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  1. Department of Zoology, Cytogenetics Laboratory, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    K K Sukla & R Raman

  2. Centre for Genetic Disorders, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    K K Sukla & R Raman

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  1. K K Sukla
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Correspondence to R Raman.

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Sukla, K., Raman, R. Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its modulation by vitamin B12 and folic acid in an Indian population. Eur J Clin Nutr 66, 111–118 (2012). https://doi.org/10.1038/ejcn.2011.152

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