Mahadevan Lakshmi, Yesudas Ancy, Sajesh P K, Revu S, Kumar Prasanna, Santhosh Devi, Santhosh Sam, Sashikumar J M, Gopalakrishnan V K, Boben Joji, Rajesh Changanamkandath
MedGenome (Division of Molecular Diagnostics), SciGenom Labs Pvt. Ltd, CSEZ, Kakkanad, Cochin, Kerala, India.
Department of Biotechnology, Karpagam University, Coimbatore, Tamil Nadu, India.
Indian J Hum Genet. 2014 Apr;20(2):175-84. doi: 10.4103/0971-6866.142896.
This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala.
Genomic DNA isolated from 100 out-patient samples from Kerala were sequenced to examine the frequency of clinically relevant polymorphisms in the genes MYBPC3 (cardiomyopathy), SLCO1B1 (statin-induced myopathy), CYP2C9, VKORC1 (response to warfarin) and CYP2C19 (response to clopidogrel).
Our analyses revealed the frequency of a 25 bp deletion variant of MYBPC3 associated with risk of cardiomyopathy was 7%, and the SLCO1B1 "C" allele associated with risk for statin-induced myopathy was 15% in this sample group. Among the other variants associated with dose-induced toxicity of warfarin, VKORC1 (c.1639G>A), was detected at 22%, while CYP2C93 and CYP2C92 alleles were present at a frequency of 15% and 3% respectively. Significantly, the tested sample population showed high prevalence (66%) of CYP2C19*2 variant, which determines response to clopidogrel therapy.
We have identified that certain variants associated with cardiovascular disease and related drug response in the five genes, especially those in VKORC1, CYP2C19 and MYBPC3, are highly prevalent in the Kerala population, with almost 2 times higher prevalence of CYP2C19*2 variant compared with other regions in the country. Since the variants chosen in this study have relevance in disease phenotype and/or drug response, and are detected at a higher frequency, this study is likely to encourage clinicians to perform genetic testing before prescribing therapy.
本研究报告了与心血管疾病风险增加相关的五种具有临床意义的变异的流行情况，以及喀拉拉邦的南印度人群中个体对常用心血管药物的不同反应。
对从喀拉拉邦100份门诊样本中分离出的基因组DNA进行测序，以检测MYBPC3（心肌病）、SLCO1B1（他汀类药物引起的肌病）、CYP2C9、VKORC1（对华法林的反应）和CYP2C19（对氯吡格雷的反应）基因中临床相关多态性的频率。
我们的分析显示，与心肌病风险相关的MYBPC3基因25 bp缺失变异的频率在该样本组中为7%，与他汀类药物引起的肌病风险相关的SLCO1B1 “C” 等位基因频率为15%。在与华法林剂量诱导毒性相关的其他变异中，VKORC1（c.1639G>A）的检测频率为22%，而CYP2C93和CYP2C92等位基因的频率分别为15%和3%。值得注意的是，受试样本群体中CYP2C19*2变异的流行率很高（66%），该变异决定了对氯吡格雷治疗的反应。
我们已经确定，在这五个基因中，某些与心血管疾病和相关药物反应相关的变异，特别是VKORC1、CYP2C19和MYBPC3中的变异，在喀拉拉邦人群中非常普遍，CYP2C19*2变异的流行率几乎是该国其他地区的2倍。由于本研究中选择的变异与疾病表型和/或药物反应相关，且检测频率较高，因此本研究可能会鼓励临床医生在开处方治疗前进行基因检测。
