同型半胱氨酸与亚甲基四氢叶酸还原酶基因型：与冠心病风险的关联以及与炎症、止血和血脂参数的关系。

Homocysteine and methylenetetrahydrofolate reductase genotype: association with risk of coronary heart disease and relation to inflammatory, hemostatic, and lipid parameters.

作者信息

Rothenbacher D, Fischer H G, Hoffmeister A, Hoffmann M M, März W, Bode G, Rosenthal J, Koenig W, Brenner H

机构信息

Department of Epidemiology, The German Centre for Research on Ageing, Heidelberg, Germany.

出版信息

Atherosclerosis. 2002 May;162(1):193-200. doi: 10.1016/s0021-9150(01)00699-2.

DOI:10.1016/s0021-9150(01)00699-2

PMID:11947914

Abstract

AIM

It has been suggested that homocysteine (tHcy) levels and methylenetetrahydrofolate reductase (MTHFR) genotype are primary risk factors for coronary heart disease (CHD). We performed a case-control study to investigate whether tHcy levels and MTHFR genotype (677 C-->T mutation and 1298 A-->C mutation) are associated with CHD under special consideration of the possibility for confounding.

METHODS

German speaking patients aged 40-68 years who underwent coronary angiography at the University of Ulm between April 1996 and November 1997 and who had at least one coronary stenosis greater than 50% were included in the study. Controls were sampled from voluntary blood donors and were matched for sex and age. tHcy levels were measured by high performance liquid chromatography and MTHFR genotype by means of polymerase chain reaction. In addition, C-reactive protein, fibrinogen, plasma viscosity, leukocytes, HDL-cholesterol and Lp(a) were determined.

RESULTS

Overall, 312 patients and 479 controls were enrolled in the study (response in patients 78%, in controls 84%). Mean tHcy value was 9.43 micromol/l in CHD patients and 8.91 micromol/l in controls (P=0.145). Prevalence of 677TT-polymorphism was 9.9% in patients and 10.4% in controls (P=0.295). Prevalence of 1298CC-polymorphism was 9.7% in patients and 13.8% in controls (P=0.346). There was a clear association of tHcy-values, but not of 677TT- or 1298CC-genotype with conventional CHD risk factors. After adjustment for these risk factors no increased risk for CHD could be associated with increased tHcy-values, with 677TT or 1298CC-genotype, or with their combination. Also no statistically significant relationships of these parameters to inflammatory, rheologic or hemostatic parameters or lipids were detectable.

CONCLUSION

These results do not confirm an independent relationship of tHcy values and MTHFR genotype with risk of CHD in the population studied.

摘要

目的

有人提出，同型半胱氨酸（总同型半胱氨酸）水平和亚甲基四氢叶酸还原酶（MTHFR）基因型是冠心病（CHD）的主要危险因素。我们进行了一项病例对照研究，以调查在特别考虑混杂因素可能性的情况下，总同型半胱氨酸水平和MTHFR基因型（677C→T突变和1298A→C突变）是否与冠心病相关。

方法

纳入1996年4月至1997年11月在乌尔姆大学接受冠状动脉造影且至少有一处冠状动脉狭窄大于50%的40 - 68岁说德语的患者。对照组从自愿献血者中抽取，并按性别和年龄进行匹配。通过高效液相色谱法测量总同型半胱氨酸水平，通过聚合酶链反应检测MTHFR基因型。此外，还测定了C反应蛋白、纤维蛋白原、血浆粘度、白细胞、高密度脂蛋白胆固醇和脂蛋白（a）。

结果

总体而言，312例患者和479例对照纳入研究（患者应答率78%，对照应答率84%）。冠心病患者的平均总同型半胱氨酸值为9.43微摩尔/升，对照组为8.91微摩尔/升（P = 0.145）。677TT多态性在患者中的患病率为9.9%，在对照组中为10.4%（P = 0.295）。1298CC多态性在患者中的患病率为9.7%，在对照组中为13.8%（P = 0.346）。总同型半胱氨酸值与传统冠心病危险因素之间存在明显关联，但677TT或1298CC基因型与传统冠心病危险因素之间无明显关联。在对这些危险因素进行调整后，总同型半胱氨酸值升高、677TT或1298CC基因型或它们的组合与冠心病风险增加无关。这些参数与炎症、血液流变学或止血参数或脂质之间也未检测到统计学上的显著关系。