Methylenetetrahydrofolate reductase 677 C -> T mutation and coronary heartdisease risk in UK Indian Asians

Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this gr oup compared with European whites. The mechanisms underlying elevated homoc ysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofol ate reductase (MTHFR) 677 C-->T mutation accounts for elevated plasma homoc ysteine and increased CHD risk in Indian Asians compared with European whit es. We investigated 454 male cases (with myocardial infarction or angiograp hically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocystei ne concentrations, MTHFR 677 C-->T genotype, and conventional CHD risk fact ors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% vers us 9.7%, P<0.001). In Indian Asians, the TT MTHFR genotype was not associat ed with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (>15 mu mol/L). In contrast, among Euro pean whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls w ith hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared wi th European white controls was accounted for by their reduced levels of B v itamins but not by the MTHFR 677T genotype. However, neither the TTMTHFR ge notype nor B vitamin levels explained the elevated homocysteine concentrati ons in CHD cases compared with controls. TTMTHFR was not a risk factor for early-onset CHD in Indian Asians (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.4; P=0.39), unlike in European whites (odds ratio, 2.1; 95% confi dence interval, 1.1 to 4.1; P=0.02). We conclude that the MTHFR 677T mutati on does not contribute to elevated plasma homocysteine concentrations or in creased CHD risk in Indian Asians compared with European whites. Our result s suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.