Tantray Javeed Ahmad, Reddy K Pratap, Jamil Kaiser, Kumar Y Shiva
Department of Zoology, Osmania University, Hyderabad, Telangana, India; Genetics Department, Bhagwan Mahavir Medical Research Centre, 10-1-1, Mahavir Marg, AC Guards, Hyderabad 500004, Telangana, India.
Department of Zoology, Osmania University, Hyderabad, Telangana, India.
Int J Cardiol. 2017 Feb 15;229:113-118. doi: 10.1016/j.ijcard.2016.11.217. Epub 2016 Nov 11.
Genetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field.
150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping. Gene expression studies for 20 CAD patients and normal controls were done by RT-PCR techniques.
In this study of patients with coronary artery disease the frequencies of the Extreme Metabolizers, Intermediate Metabolizers in CYP2C192 (rs4244285) were present in 90% and 10% but no Poor Metabolizers were found in this allele. The frequencies of Extreme Metabolizer, Intermediate Metabolizer and Poor Metabolizer in CYP2C193 (rs4986893) were present in 41%, 50% and 9% respectively. Among 20 CAD samples, 13 of 20 (65%) showed CYP2C19 gene over expression in CAD patients and all controls showed normal expression. Among the 150 CAD patients, 145 had normal karyotype, only five patients showed change in normal karyogram carried out by leukocyte culture.
Genetic testing of CYP2C19 may help in prescribing a dose according to genetic makeup and represent the initial steps towards the development of diagnostic tests and therapeutic strategies that will substantially improve human health. This study highlights the progress that has been made in using pharmacogenomic and gene expression analysis, cardiovascular genomic research and the potential for applying these findings in clinical medicine.
遗传因素在大多数心脏疾病的发病机制中起着重要作用。本研究旨在将冠状动脉疾病与人口统计学、生化改变、单核苷酸多态性、基因表达及染色体异常相关联，以进一步启发该领域的研究。
选取150例服用氯吡格雷的患者，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术进行单核苷酸多态性分析。对同一批患者的白细胞培养物进行核型分析以进行细胞遗传学研究。采用逆转录聚合酶链反应（RT-PCR）技术对20例冠心病患者和正常对照进行基因表达研究。
在本项针对冠心病患者的研究中，CYP2C192（rs4244285）基因的超快代谢者和中速代谢者频率分别为90%和10%，但该等位基因中未发现慢代谢者。CYP2C193（rs4986893）基因的超快代谢者、中速代谢者和慢代谢者频率分别为41%、50%和9%。在20例冠心病样本中，20例中有13例（65%）显示冠心病患者CYP2C19基因过度表达，而所有对照均显示正常表达。在150例冠心病患者中，145例核型正常，仅5例患者经白细胞培养进行的核型分析显示核型有改变。
CYP2C19基因检测有助于根据基因组成来确定用药剂量，是朝着开发能显著改善人类健康的诊断测试和治疗策略迈出的第一步。本研究突出了在利用药物基因组学和基因表达分析、心血管基因组研究方面所取得的进展以及将这些发现应用于临床医学的潜力。
