© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Methylenetetrahydrofolate Reductase 677 C
T Mutation and Coronary Heart Disease Risk in UK Indian Asians
From the National Heart and Lung Institute (J.C.C., P.R., J.S.K.), Imperial College School of Medicine, Hammersmith Hospital; the Department of Haematology (H.I., E.T., D.L.), Imperial College School of Medicine, Charing Cross Hospital; and the Department of Human Nutrition (O.A.O.), St Bartholomew’s and Royal London School of Medicine & Dentistry, Queen Mary and Westfield College, London, UK; and the Department of Pharmacology (H.R., P.U.), University of Bergen, Armauer Hansen Hus, Bergen, Norway.
Correspondence to Dr J.S. Kooner, MD, FRCP, Senior Lecturer and Consultant Cardiologist, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. E-mail j.kooner{at}ic.ac.uk
Abstract—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
CT 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
µmol/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 TT MTHFR genotype nor B vitamin
levels explained the elevated homocysteine concentrations in CHD cases
compared with controls. TT MTHFR 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.
Key Words: arteriosclerosis • genetics • nutrition
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