年轻女性心肌梗死与血浆总同型半胱氨酸、叶酸及亚甲基四氢叶酸还原酶基因常见变异的关系

Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene.

作者信息

Schwartz S M, Siscovick D S, Malinow M R, Rosendaal F R, Beverly R K, Hess D L, Psaty B M, Longstreth W T, Koepsell T D, Raghunathan T E, Reitsma P H

机构信息

Department of Epidemiology, University of Washington, Seattle 98101, USA.

出版信息

Circulation. 1997 Jul 15;96(2):412-7. doi: 10.1161/01.cir.96.2.412.

DOI:10.1161/01.cir.96.2.412

PMID:9244205

Abstract

BACKGROUND

In a population-based study, we examined the relationship between the risk of myocardial infarction (MI) among young women and plasma total homocysteine (tHCY), folate, vitamin B12, and a common cytosine (C) to thymine (T) polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR).

METHODS AND RESULTS

In-person interviews and nonfasting blood samples were obtained from 79 women < 45 years old diagnosed with MI and 386 demographically similar control subjects living in western Washington state between 1991 and 1995. Compared with control subjects, case patients had higher mean tHCY concentrations (13.4+/-5.2 versus 11.1+/-4.4 micromol/L, P=.0004) and lower mean folate concentrations (12.4+/-13.4 versus 16.1+/-12.2 nmol/L, P=.018). There was no difference in vitamin B12 concentrations between case patients and control subjects (346.8+/-188.4 versus 349.7+/-132.4 pmol/L, P=.90). After adjusting for cardiovascular risk factors, we found that women with tHCY > or = 15.6 micromol/L were at approximately twice the risk of MI as women with tHCY < 10.0 micromol/L (OR, 2.3; 95% CI, 0.94 to 5.64). Women with folate > or = 8.39 nmol/L had an approximately 50% lower risk of MI than women with folate < 5.27 nmol/L (OR, 0.54; 95% CI, 0.23 to 1.28). There was no association with vitamin B12 concentration. Among control subjects, 12.7% were homozygous for the MTHFR T677 allele, and these women had higher plasma tHCY and lower plasma folate than women with other genotypes. Ten percent of case patients were homozygous for the T677 allele, and there was no association of homozygosity for T677 with MI risk (OR, 0.90; 95% CI, 0.31 to 2.29).

CONCLUSIONS

These data support the hypothesis that elevated plasma tHCY and low plasma folate are risk factors for MI among young women. Although homozygosity for MTHFR T677 is related to increased plasma tHCY and low plasma folate, this genetic characteristic is not a risk factor for MI in this population.

摘要

背景

在一项基于人群的研究中，我们研究了年轻女性心肌梗死（MI）风险与血浆总同型半胱氨酸（tHCY）、叶酸、维生素B12以及5,10-亚甲基四氢叶酸还原酶（MTHFR）基因中常见的胞嘧啶（C）到胸腺嘧啶（T）多态性之间的关系。

方法与结果

1991年至1995年间，对华盛顿州西部79名年龄小于45岁且被诊断为心肌梗死的女性以及386名人口统计学特征相似的对照受试者进行了面对面访谈并采集了非空腹血样。与对照受试者相比，病例患者的平均tHCY浓度更高（13.4±5.2对11.1±4.4 μmol/L，P = 0.0004），平均叶酸浓度更低（12.4±13.4对16.1±12.2 nmol/L，P = 0.018）。病例患者与对照受试者之间的维生素B12浓度无差异（346.8±188.4对349.7±132.4 pmol/L，P = 0.90）。在调整心血管危险因素后，我们发现tHCY≥15.6 μmol/L的女性患心肌梗死的风险约为tHCY＜10.0 μmol/L女性的两倍（OR，2.3；95%CI，0.94至5.64）。叶酸≥8.39 nmol/L的女性患心肌梗死的风险比叶酸＜5.27 nmol/L的女性低约50%（OR，0.54；95%CI，0.23至1.28）。与维生素B12浓度无关。在对照受试者中，12.7%为MTHFR T677等位基因纯合子，这些女性的血浆tHCY较高，血浆叶酸较低，比其他基因型的女性高。10%的病例患者为T677等位基因纯合子，T677纯合性与心肌梗死风险无关（OR，0.90；95%CI，0.31至2.29）。