Methylenetetrahydrofolate reductase 677 C→T mutation and coronary heart disease risk in UK Indian Asians

被引:50
作者
Chambers, JC
Ireland, H
Thompson, E
Reilly, P
Obeid, OA
Refsum, H
Ueland, P
Lane, DA
Kooner, JS
机构
[1] Hammersmith Hosp, Imperial Coll, Sch Med, Natl Heart & Lung Inst, London W12 0NN, England
[2] Charing Cross Hosp, Imperial Coll, Sch Med, Dept Haematol, London, England
[3] Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, Dept Human Nutr, London E1 4NS, England
[4] Univ Bergen, Armauer Hansen Hus, Dept Pharmacol, Bergen, Norway
关键词
arteriosclerosis; genetics; nutrition;
D O I
10.1161/01.ATV.20.11.2448
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this group compared with European whites. The mechanisms underlying elevated homocysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) 677 C-->T mutation accounts for elevated plasma homocysteine and increased CHD risk in Indian Asians compared with European whites. We investigated 454 male cases (with myocardial infarction or angiographically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocysteine concentrations, MTHFR 677 C-->T genotype, and conventional CHD risk factors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% versus 9.7%, P<0.001). In Indian Asians, the TT MTHFR genotype was not associated with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (>15 mu mol/L). In contrast, among European whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls with hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared with European white controls was accounted for by their reduced levels of B vitamins but not by the MTHFR 677T genotype. However, neither the TTMTHFR genotype nor B vitamin levels explained the elevated homocysteine concentrations 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% confidence interval, 1.1 to 4.1; P=0.02). We conclude that the MTHFR 677T mutation does not contribute to elevated plasma homocysteine concentrations or increased CHD risk in Indian Asians compared with European whites. Our results suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.
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收藏
页码:2448 / 2452
页数:5
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