Kumar Jitender, Garg Gaurav, Kumar Arun, Sundaramoorthy Elayanambi, Sanapala Krishna Rao, Ghosh Saurabh, Karthikeyan Ganesan, Ramakrishnan Lakshmy, Sengupta Shantanu
Institute of Genomics and Integrative Biology, Delhi, India.
Circ Cardiovasc Genet. 2009 Dec;2(6):599-606. doi: 10.1161/CIRCGENETICS.108.841411. Epub 2009 Sep 5.
An elevated level of homocysteine (hyperhomocysteinemia) has been implicated as an independent risk factor for cardiovascular diseases. Deficiency of dietary factors like vitamin B(12), folate, and genetic variations can cause hyperhomocysteinemia. The prevalence of hyperhomocysteinemia in the Indian population is likely to be high because most Indians adhere to a vegetarian diet, deficient in vitamin B(12). In the
deficiency, variations in genes involved in homocysteine metabolism might have a greater impact on homocysteine levels.
We genotyped 44 nonsynonymous single-nucleotide polymorphisms (nsSNPs) from 11 genes involved in homocysteine metabolism and found only 14 to be polymorphic. These 14 nsSNPs were genotyped in 546 individuals recruited from a tertiary care center in New Delhi, India, and it was found that choline dehydrogenase (CHDH A119C) and methylenetetrahydrofolate reductase (MTHFR C677T) were significantly associated with plasma total homocysteine levels (P=0.009 and P=0.001, respectively). These 2 SNPs were further genotyped in 330 individuals recruited from the same center, and the association remained significant even after increasing the sample size. Furthermore, we found the possibility of a significant interaction between vegetarian diet and the 2 polymorphisms that could explain the variation of homocysteine levels. We also genotyped all the polymorphic nsSNPs in apparently healthy individuals recruited from 24 different subpopulations (based on their linguistic lineage) spread across the country to determine their basal frequencies. The frequencies of these SNPs varied significantly between linguistic groups.
Vegetarian diet along with CHDH A119C and MTHFR C677T play an important role in modulating the homocysteine levels in Indian population.
同型半胱氨酸水平升高（高同型半胱氨酸血症）被认为是心血管疾病的独立危险因素。饮食中缺乏维生素B12、叶酸等因素以及基因变异可导致高同型半胱氨酸血症。印度人群中高同型半胱氨酸血症的患病率可能较高，因为大多数印度人坚持素食，缺乏维生素B12。在这种缺乏的情况下，参与同型半胱氨酸代谢的基因变异可能对同型半胱氨酸水平有更大影响。
我们对参与同型半胱氨酸代谢的11个基因中的44个非同义单核苷酸多态性（nsSNP）进行基因分型，发现只有14个具有多态性。在从印度新德里一家三级医疗中心招募的546名个体中对这14个nsSNP进行基因分型，发现胆碱脱氢酶（CHDH A119C）和亚甲基四氢叶酸还原酶（MTHFR C677T）与血浆总同型半胱氨酸水平显著相关（分别为P = 0.009和P = 0.001）。在从同一中心招募的330名个体中对这2个SNP进一步进行基因分型，即使增加样本量后这种关联仍然显著。此外，我们发现素食饮食与这2种多态性之间存在显著相互作用的可能性，这可以解释同型半胱氨酸水平的变化。我们还对从全国24个不同亚群体（基于语言谱系）招募的明显健康个体中的所有多态性nsSNP进行基因分型，以确定它们的基础频率。这些SNP的频率在不同语言群体之间有显著差异。
素食饮食以及CHDH A119C和MTHFR C677T在调节印度人群同型半胱氨酸水平方面起重要作用。
