Nakata Y, Katsuya T, Takami S, Sato N, Fu Y, Ishikawa K, Takiuchi S, Rakugi H, Miki T, Higaki J, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Am J Hypertens. 1998 Aug;11(8 Pt 1):1019-23. doi: 10.1016/s0895-7061(98)00046-6.
Hyperhomocysteinemia is reported to be associated with an increase in the incidence of ischemic heart disease and cerebrovascular disease. Genetic aberrations in methylenetetrahydrofolate reductase (MTHFR) may account for reduced enzyme activity and elevated plasma homocysteine level. A recent report revealed that a common mutation (677C to T; Ala to Val) in the MTHFR gene is associated with decreased specific MTHFR activity and with increased risk for coronary artery disease in the homozygous state (Val/Val). In the present study, we investigated whether the MTHFR gene is a genetic risk factor for cerebrovascular disease (CVD). To undertake a case-control study, we selected the patients with cerebral infarction (n = 48) or cerebral hemorrhage (n = 35) and examined the association between MTHFR gene polymorphism and CVD. The genotype distribution of the MTHFR gene was not significantly different between cases and controls. Because the possibility of matching the morbidity of the effects of hypertension, the lack of association could not be excluded in the first study; however, we also examined whether the MTHFR mutation was associated with any clinical risk factor for CVD or with hypertension. It turned out that the subjects with the Val allele of the MTHFR gene had significantly lower blood pressure than the subjects with other genotypes in the general population (P = .02), and that the frequency of the Val/Val genotype in hypertensive subjects (n = 173) was significantly lower than in control subjects (n = 184) (P = .03). From these results, we conclude that the Val/Val homozygous state of the MTHFR gene increased the risk of thrombosis, but reduced the blood pressure, which resulted in the lack of increased risk for CVD.
据报道，高同型半胱氨酸血症与缺血性心脏病和脑血管疾病发病率的增加有关。亚甲基四氢叶酸还原酶（MTHFR）的基因异常可能导致酶活性降低和血浆同型半胱氨酸水平升高。最近的一份报告显示，MTHFR基因中的一个常见突变（677C突变为T；丙氨酸突变为缬氨酸）与特定MTHFR活性降低以及纯合状态（Val/Val）下患冠状动脉疾病的风险增加有关。在本研究中，我们调查了MTHFR基因是否是脑血管疾病（CVD）的遗传危险因素。为了进行病例对照研究，我们选择了脑梗死患者（n = 48）或脑出血患者（n = 35），并研究了MTHFR基因多态性与CVD之间的关联。病例组和对照组之间MTHFR基因的基因型分布没有显著差异。由于存在与高血压效应发病率匹配的可能性，在第一项研究中不能排除缺乏关联的情况；然而，我们还研究了MTHFR突变是否与CVD的任何临床危险因素或高血压有关。结果发现，在普通人群中，携带MTHFR基因Val等位基因的受试者血压显著低于其他基因型的受试者（P = .02），并且高血压患者（n = 173）中Val/Val基因型的频率显著低于对照组（n = 184）（P = .03）。根据这些结果，我们得出结论，MTHFR基因的Val/Val纯合状态增加了血栓形成的风险，但降低了血压，这导致CVD风险没有增加。
