Bosco Paolo, Guéant-Rodriguez Rosa-Maria, Anello Guido, Spada Rosario, Romano Antonino, Fajardo Adrian, Caraci Filippo, Ferri Raffaele, Guéant Jean-Louis
IRCCS Associazione Oasi Maria S.S.- Institute for Research on Mental Retardation and Brain Aging, 94018 Troina (EN), Italy.
Thromb Haemost. 2006 Aug;96(2):154-9.
Association between methylenetetrahydrofolate reductase polymorphism (MTHFR 677 C>T ), a determinant of homocysteine plasma level (t-Hcys), with ischaemc cerebrovascular disease (iCVD) seems to be neutral in North Europe and North America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of methionine synthase reductase (MTRR) and 776 C>G of transcobalamin ( TCN2 ) needs to be evaluated further. It was the objective of this study to evaluate the association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with iCVD, in an Italian population from Sicily. We investigated the association of these polymorphisms, t-Hcys, vitamin B12 and folate with iCVD in 252 subjects, including 131 cases and 121 sex- and age-matched healthy controls. t-Hcys was higher in the iCVD group than in controls [15.3 (11.5 - 17.9) vs. 11.6 (9.4 - 14.5) microM; P = 0.0007] and also in subjects with TCN2 776CG genotype, compared to homozygous genotypes [13.5 (9.9 +/- 16.9) vs. 11.7 (9.6 +/- 14.4) microM; P = 0.0327]. The folate level in cases and controls was consistent with an adequate dietary intake [12.7 (9.0 - 15.3) vs. 12.5 (9.6 - 16.9) nM; P = 0.7203]. In multivariate analysis, t-Hcys was a significant independent predictor of iCVD with an odds ratio of 1.14 (95 % C.I.: 1.06 - 1.24; P = 0.0006). No association was found between MTHFR, MTR, MTRR and TCN2 polymorphisms and iCVD risk. We have found an influence of t-Hcys and a neutral effect of MTHFR, MTR, MTRR and TCN2 on iCVD risk in Sicily. The neutral influence of these polymorphisms may be explained by adequate status in folate and vitamin B12. Other factors underlying the increased t-Hcys need further investigations.
亚甲基四氢叶酸还原酶多态性（MTHFR 677 C>T）作为血浆同型半胱氨酸水平（总同型半胱氨酸，t-Hcys）的一个决定因素，与缺血性脑血管疾病（iCVD）之间的关联在北欧和北美似乎呈中性。甲硫氨酸合酶（MTR）的2756 A>G、甲硫氨酸合酶还原酶（MTRR）的66 A>G以及转钴胺素（TCN2）的776 C>G之间的关联需要进一步评估。本研究的目的是在西西里岛的意大利人群中评估这些多态性、t-Hcys、维生素B12和叶酸水平与iCVD之间的关联。我们在252名受试者中调查了这些多态性、t-Hcys、维生素B12和叶酸与iCVD之间的关联，其中包括131例病例和121名年龄和性别匹配的健康对照。iCVD组的t-Hcys高于对照组[15.3（11.5 - 17.9）对11.6（9.4 - 14.5）微摩尔；P = 0.0007]，与纯合子基因型相比，TCN2 776CG基因型的受试者中t-Hcys也更高[13.5（9.9 +/- 16.9）对11.7（9.6 +/- 14.4）微摩尔；P = 0.0327]。病例组和对照组的叶酸水平与充足的饮食摄入量一致[12.7（9.0 - 15.3）对12.5（9.6 - 16.9）纳摩尔；P = 0.7203]。在多变量分析中，t-Hcys是iCVD的一个显著独立预测因子，优势比为1.14（95%置信区间：1.06 - 1.24；P = 0.0006）。未发现MTHFR、MTR、MTRR和TCN2多态性与iCVD风险之间存在关联。我们发现在西西里岛t-Hcys对iCVD风险有影响，而MTHFR、MTR、MTRR和TCN2对iCVD风险呈中性作用。这些多态性的中性影响可能由叶酸和维生素B12的充足状态来解释。t-Hcys升高的其他潜在因素需要进一步研究。
