Meleady Raymond, Ueland Per M, Blom Henk, Whitehead Alexander S, Refsum Helga, Daly Leslie E, Vollset Stein Emil, Donohue Cait, Giesendorf Belinda, Graham Ian M, Ulvik Arve, Zhang Ying, Bjorke Monsen Anne-Lise
Department of Cardiology, Adelaide-Meath Hospital, Incorporating the National Children's Hospital, Tallaght, Dublin, Ireland.
Am J Clin Nutr. 2003 Jan;77(1):63-70. doi: 10.1093/ajcn/77.1.63.
Homozygotes for the thermolabile mutation (TT genotype) of the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme have elevated plasma concentrations of the cardiovascular disease risk factor homocysteine, particularly if folate depleted.
We examined the relations between thermolabile MTHFR, plasma homocysteine, plasma folate, and vascular disease risk.
This was a case-control comparison in 711 vascular disease cases and 747 controls from 9 European countries.
The TT genotype was associated with higher homocysteine and lower plasma folate than the CC and CT genotypes in both cases and controls and a nonsignificant increase in vascular disease risk (1.26; 95% CI: 0.88, 1.81; P = 0.20). The frequency of the TT genotype in cases was not significantly different from that in controls (12.8% compared with 10.8%). After adjustment for traditional risk factors, the TT genotype was associated with an odds ratio of 1.48 (1.0, 2.20) for risk of vascular disease. This risk was attenuated after further adjustment for homocysteine. In subgroups with homocysteine concentrations >or= 9 micro mol/L, risk tended to be higher in CC than in TT subjects. However, CC subjects were characterized by a higher prevalence of the conventional risk factors associated with both elevated plasma homocysteine and serum creatinine. After adjustment, the risk of vascular disease associated with each genotype was not significantly different.
There was a strong graded association between homocysteine and vascular risk in all genotypes. MTHFR genotype is a key determinant of plasma total homocysteine concentrations. The initially nonsignificant risk estimate associated with the TT genotype was strengthened after adjustment for conventional cardiovascular disease risk factors but was attenuated after adjustment for plasma folate and total homocysteine. The modest risk increase conferred by the TT genotype is mediated mainly by increased total homocysteine and low plasma folate concentrations.
亚甲基四氢叶酸还原酶（MTHFR；EC 1.5.1.20）酶的不耐热突变纯合子（TT基因型）会提高心血管疾病风险因素同型半胱氨酸的血浆浓度，尤其是在叶酸缺乏的情况下。
我们研究了不耐热MTHFR、血浆同型半胱氨酸、血浆叶酸与血管疾病风险之间的关系。
这是一项对来自9个欧洲国家的711例血管疾病病例和747例对照进行的病例对照比较研究。
在病例组和对照组中，TT基因型与CC和CT基因型相比，同型半胱氨酸水平更高，血浆叶酸水平更低，血管疾病风险有不显著增加（1.26；95%可信区间：0.88，1.81；P = 0.20）。病例组中TT基因型的频率与对照组无显著差异（分别为12.8%和10.8%）。在对传统风险因素进行调整后，TT基因型与血管疾病风险的比值比为1.48（1.0，2.20）。在进一步对同型半胱氨酸进行调整后，这种风险有所减弱。在同型半胱氨酸浓度≥9微摩尔/升的亚组中，CC基因型受试者的风险往往高于TT基因型受试者。然而，CC基因型受试者的特点是与血浆同型半胱氨酸和血清肌酐升高相关的传统风险因素患病率更高。调整后，各基因型与血管疾病相关的风险无显著差异。
在所有基因型中，同型半胱氨酸与血管风险之间存在强烈的分级关联。MTHFR基因型是血浆总同型半胱氨酸浓度的关键决定因素。在对传统心血管疾病风险因素进行调整后，最初与TT基因型相关的不显著风险估计值得到加强，但在对血浆叶酸和总同型半胱氨酸进行调整后有所减弱。TT基因型带来的适度风险增加主要由总同型半胱氨酸增加和血浆叶酸浓度降低介导。
