Miriuka Santiago G, Langman Loralie J, Evrovski Jovan, Miner Steven E S, D'Mello Nisha, Delgado Diego H, Wong Betty Y L, Ross Heather J, Cole David E C
Department of Medicine, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.
Transpl Int. 2005 Jan;18(1):29-35. doi: 10.1111/j.1432-2277.2004.00021.x.
Genetic determinants for high homocysteine (Hcy) levels are now well known. We studied several single nucleotide polymorphisms (SNP) in Hcy-regulating genes [methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C; methionine synthase (MS) A2756G; methionine synthase reductase (MTRR) A66G] in relation to total plasma Hcy levels, transplant coronary artery disease and thromboembolic episodes in 84 heart transplant patients, and we compared the incidence of these polymorphisms with those in a healthy adult controls. At least one copy of the G allele of the MTRR A66G SNP was found in a significantly greater proportion of cardiac transplant (CTX) recipients compared with controls (94.0% vs. 79.9% respectively). None of the SNP analyzed were correlated with total Hcy plasma levels or the presence of transplant coronary artery disease. However, MS A2756G was significantly associated with cobalamin levels (AA genotype: 290 +/- 122 pmol/l; AG: 381 +/- 151 pmol/l and GG: 415 +/- 100 pmol/l), as was MTRR A66G (AA: 478 +/- 219 pmol/l, AG: 306 +/- 124 pmol/l and GG: 306 +/- 123 pmol/l). MTRR A66G was also correlated with serum folate. No association was found with thromboembolic events. In conclusion, there was a significant difference in the frequency of the G allele genotype of the MTRR A66G in CTX patients versus controls. Differences in cobalamin and folate levels with the MTRR A66G and MS A2756G polymorphisms were noted. Thus, SNP in Hcy-regulating genes may be important determinants of vitamin metabolism in CTX, raising the question of increased vitamin requirements to minimize increased plasma Hcy in this high-risk group.
高同型半胱氨酸（Hcy）水平的遗传决定因素现已为人熟知。我们研究了84例心脏移植患者中Hcy调节基因[亚甲基四氢叶酸还原酶（MTHFR）C677T和A1298C；蛋氨酸合成酶（MS）A2756G；蛋氨酸合成酶还原酶（MTRR）A66G]中的几个单核苷酸多态性（SNP）与血浆总Hcy水平、移植后冠状动脉疾病和血栓栓塞事件的关系，并将这些多态性的发生率与健康成人对照组进行了比较。与对照组相比，心脏移植（CTX）受者中MTRR A66G SNP的G等位基因至少有一个拷贝的比例显著更高（分别为94.0%和79.9%）。分析的SNP均与血浆总Hcy水平或移植后冠状动脉疾病的存在无关。然而，MS A2756G与钴胺素水平显著相关（AA基因型：290±122 pmol/l；AG：381±151 pmol/l和GG：415±100 pmol/l），MTRR A66G也是如此（AA：478±219 pmol/l，AG：306±124 pmol/l和GG：306±123 pmol/l）。MTRR A66G也与血清叶酸相关。未发现与血栓栓塞事件有关联。总之，CTX患者与对照组相比，MTRR A66G的G等位基因基因型频率存在显著差异。注意到MTRR A66G和MS A2756G多态性与钴胺素和叶酸水平的差异。因此，Hcy调节基因中的SNP可能是CTX中维生素代谢的重要决定因素，这就提出了在这个高危群体中增加维生素需求量以尽量减少血浆Hcy升高的问题。
