亚甲基四氢叶酸还原酶基因型在家族性和多基因高胆固醇血症中与心血管风险的不同关系。

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

作者信息

Wierzbicki A S, Lambert-Hammill M, Junadi E, Lumb P J, Crook M A

机构信息

Department of Chemical Pathology, King's College (Guy's, King's and St. Thomas' Medical School), St Thomas' Hospital Campus, London, UK.

出版信息

J Cardiovasc Risk. 2000 Dec;7(6):431-4. doi: 10.1177/204748730000700607.

DOI:10.1177/204748730000700607

PMID:11155296

Abstract

BACKGROUND

Plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism have been suggested as being risk factors for cardiovascular disease.

OBJECTIVE

To determine whether plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism are risk factors for coronary heart disease in patients with heterozygous familial hypercholesterolaemia as compared with those with polygenic hyperlipidaemia.

METHODS

Plasma homocysteine and the methylene tetrahydrofolate reductase polymorphism were assessed with other risk factors in 112 patients with familial hypercholesterolaemia and 72 patients with polygenic hyperlipidaemia, of 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 familial hypercholesterolaemia or polygenic hyperlipidaemia compared with controls. The allele frequencies for C677T were significantly different in patients with coronary heart disease and with polygenic hyperlipidaemia (0.35 versus 0.29) (P = 0.02) as opposed to those with coronary heart disease and familial hypercholesterolaemia (0.25 versus 0.30) (P = 0.63). Methylene tetrahydrofolate reductase genotype but not homocysteine had a weak association with coronary heart disease in logistic regression analysis in patients with polygenic hyperlipidaemia (P = 0.05) but neither methylene tetrahydrofolate reductase genotype or plasma homocysteine was a risk factor in patients with familial hypercholesterolaemia.

CONCLUSION

Whilst methylene tetrahydrofolate reductase genotype may be a weak risk factor for coronary heart disease in polygenic hyperlipidaemia as opposed to familial hypercholesterolaemia, homocysteine does not seem to be an important risk factor for coronary heart disease in patients in southern UK.

摘要

背景

血浆同型半胱氨酸及亚甲基四氢叶酸还原酶C677T多态性被认为是心血管疾病的危险因素。

目的

确定与多基因高脂血症患者相比，杂合子家族性高胆固醇血症患者的血浆同型半胱氨酸及亚甲基四氢叶酸还原酶C677T多态性是否为冠心病的危险因素。

方法

对112例家族性高胆固醇血症患者、72例多基因高脂血症患者及100例健康正常受试者的血浆同型半胱氨酸、亚甲基四氢叶酸还原酶多态性及其他危险因素进行评估。其中，家族性高胆固醇血症患者和多基因高脂血症患者中分别有29例（25.8%）和30例（41%）已确诊患有心血管疾病。

结果

与对照组相比，家族性高胆固醇血症或多基因高脂血症患者中，无论有无冠心病，其血浆同型半胱氨酸均未显著升高。冠心病合并多基因高脂血症患者与冠心病合并家族性高胆固醇血症患者的C677T等位基因频率存在显著差异（分别为0.35对0.29）（P = 0.02），而冠心病合并家族性高胆固醇血症患者之间的等位基因频率差异不显著（0.25对0.30）（P = 0.63）。在多基因高脂血症患者的逻辑回归分析中，亚甲基四氢叶酸还原酶基因型与冠心病存在弱关联（P = 0.05），但同型半胱氨酸与冠心病无关联；在家族性高胆固醇血症患者中，亚甲基四氢叶酸还原酶基因型和血浆同型半胱氨酸均不是危险因素。