Differing relationships of methylene tetrahydrofolate reductase genotypes with cardiovascular risk in familiar and polygenic hypercholesterolaemia

Background Plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism have been suggested as being risk factors for cardiovas cular disease. Objective To determine whether plasma homocysteine and the methylene tetrah ydrofolate reductase C677T polymorphism are risk factors for coronary heart disease in patients with heterozygous familial hypercholesterolaemia as co mpared with those with polygenic hyperlipidaemia. Methods Plasma homocysteine and the methylene tetrahydrofolate reductase po lymorphism were assessed with other risk factors in 112 patients with famil ial hypercholesterolaemia and 72 patients with polygenic hyperlipidaemia, o f whom 29 (25.8%) and 30 (41%) respectively had established cardiovascular disease and in 100 healthy normal subjects. Results Plasma homocysteine was not significantly elevated in patients with and without coronary heart disease with familiar hypercholesterolaemia or polygenic hyperlipidaemia compared with controls. The allele frequencies fo r C677T were significantly different in patients with coronary heart diseas e and with polygenic hyperlipidaemia (0.35 versus 0.29) (P = 0.02) as oppos ed to those with coronary heart disease and familial bypercholesterolaemia (0.25 versus 0.30) (P = 0.63). Methylene tetrahydrofolate reductase genotyp e but not homocysteine had a weak association with coronary heart disease i n logistic regression analysis in patients with polygenic hyperlipidaemia(P = 0.05) but neither methylene tetrahydrofolate reductase genotype or plasm a homocysteine was a risk factor in patients with familial hypercholesterol aemia. Conclusion Whilst methylene tetrahydrofolate reductase genotype may be a we ak risk factor for coronary heart disease in polygenic hyperlipidaemia as o pposed to familial hypercholesterolaemia, homocysteine does not seem to be an important risk factor for coronary heart disease in patients in southern UK. J Cardiovasc Risk 7:431-434 (C) 2000 Lippincott Williams & Wilkins.