Iqbal Mohammad Perwaiz, Iqbal Khalida, Tareen Asal Khan, Parveen Siddiqa, Mehboobali Naseema, Haider Ghulam, Iqbal Saleem Perwaiz
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
National Institute of Cardiovascular Diseases, Karachi, Pakistan.
Pak J Pharm Sci. 2016 Nov;29(6):1901-1906.
High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age <45 years) and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23±17.2 and 23±13.4 μmol/l, respectively which are higher than the upper normal limit of this biomarker (15μmol/l). MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine (p value <0.05), while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.
与其他人群相比，巴基斯坦人过早患冠心病的比例较高，这表明该人群具有患这种疾病的遗传易感性。由于巴基斯坦尚未开展研究同型半胱氨酸循环相关基因多态性之间关系的调查，本研究的目的是确定在患有过早急性心肌梗死（AMI）的巴基斯坦患者群体中，亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C；蛋氨酸合酶（MS）A2756G；胱硫醚-β-合酶（CBS）844ins68、G919A多态性与过早急性心肌梗死之间是否存在关联。在一项横断面研究中，使用PCR-RFLP方法对143例AMI患者（年龄<45岁）和153例健康对照的DNA样本进行上述多态性基因分型。对患者和健康对照的血浆/血清样本进行同型半胱氨酸、叶酸和维生素B12筛查。采用单因素方差分析和卡方检验进行数据分析。发现过早AMI患者和健康对照的平均血浆同型半胱氨酸水平分别为23±17.2和23±13.4μmol/l，均高于该生物标志物的正常上限（15μmol/l）。发现健康对照中的MTHFR 677 CT基因型和AMI患者中的MTHFR 677 TT基因型血浆同型半胱氨酸水平显著升高（p值<0.05），而所有其他多态性在AMI患者和健康对照之间的同型半胱氨酸平均水平上未显示任何显著差异。此外，在该人群中未观察到MTHFR C677T、A1298C；MS A2756C；CBS844ins68多态性与过早AMI之间存在关联。这表明MTHFR、MS和CBS基因中的常见多态性在巴基斯坦人群过早AMI中不起作用。
