Iqbal M Perwaiz, Fatima Tasneem, Parveen Siddiqa, Yousuf Farzana A, Shafiq Majid, Mehboobali Naseema, Khan Abrar H, Azam Iqbal, Frossard Philippe M
Department of Biological and Biomedical Sciences, Aga Khan University, Stadium Road, P.O. Box-3500, Karachi-74800, Pakistan.
J Mol Genet Med. 2005 Jul 28;1(1):26-32. doi: 10.4172/1747-0862.1000007.
Pakistanis belong to the South Asian population which has the highest known rate of coronary artery disease. Folic acid deficiency also appears to be highly prevalent in this population. Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism decreases the activity of this enzyme and can be associated with mild to moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with coronary artery disease. To assess the value of genotyping the MTHFR 677C>T dimorphism, we carried out a case-control study of dimorphism 677C>T for putative association with myocardial infarction (MI) among Pakistani nationals. We investigated a sample population of 622 Pakistanis consisting of 225 controls and 397 patients with clinical diagnosis of acute MI (AMI). MTHFR C677T alleles were determined by assays based on polymerase chain reaction and restriction endonuclease analysis. Frequencies of C alleles were 0.87 among controls and 0.86 among AMI patients. The MTHFR 677C>T dimorphism showed no association with MI (chi(2) = 0.25, 1df, P=0.62), serum levels of folate and vitamin B12 and plasma level of vitamin B6. A significant association, however, was found between homozygous 677T genotype and plasma levels of homocysteine. Multivariate analysis of the data showed that in case of log homocysteine, age and MTHFR genotypes were significantly different (P<0.001). In case of B12, smoking and age were found to be statistically significant (P<0.001), while in case of serum folate only smoking was found to be significant (P<0.001). The results indicate that MTHFR 677C>T polymorphism, though associated with homocysteine levels, confers no significant risk of coronary artery disease in the Pakistani population investigated here. We suggest that the higher incidence of AMI in South Asia occurs through mechanisms other than the MTHFR related pathways.
巴基斯坦人属于南亚人群，该人群已知患冠状动脉疾病的比例最高。叶酸缺乏在这一人群中似乎也非常普遍。亚甲基四氢叶酸还原酶（MTHFR）677C>T多态性会降低该酶的活性，在纯合子中可能与轻度至中度高同型半胱氨酸血症有关，尤其是在存在叶酸缺乏的情况下，也与冠状动脉疾病有关。为了评估对MTHFR 677C>T二态性进行基因分型的价值，我们对巴基斯坦国民中677C>T二态性与心肌梗死（MI）的假定关联进行了一项病例对照研究。我们调查了622名巴基斯坦人的样本群体，其中包括225名对照者和397名临床诊断为急性心肌梗死（AMI）的患者。MTHFR C677T等位基因通过基于聚合酶链反应和限制性内切酶分析的检测方法来确定。C等位基因在对照者中的频率为0.87，在AMI患者中的频率为0.86。MTHFR 677C>T二态性与MI（χ² = 0.25，1自由度，P = 0.62）、血清叶酸和维生素B12水平以及血浆维生素B6水平均无关联。然而，在纯合677T基因型与同型半胱氨酸血浆水平之间发现了显著关联。对数据的多变量分析表明，就对数同型半胱氨酸而言，年龄和MTHFR基因型存在显著差异（P < 0.001）。就维生素B12而言，吸烟和年龄具有统计学意义（P < 0.001），而就血清叶酸而言，仅吸烟具有显著意义（P < 0.001）。结果表明，MTHFR 677C>T多态性虽然与同型半胱氨酸水平有关，但在本研究的巴基斯坦人群中并未赋予冠状动脉疾病显著风险。我们认为，南亚地区AMI发病率较高是通过与MTHFR相关途径不同的机制发生的。
