Allahdini Mojgan, Kamalidehghan Behnam, Akbari Leila, Azadfar Parisa, Rahmani Ali, Ahmadipour Fatemeh, Meng Goh Yong, Masserrat Abbas, Houshmand Massoud
Department of Molecular Biology, Ahar Branch Islamic Azad University, Ahar, Iran.
Pharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Drug Des Devel Ther. 2015 Oct 28;9:5835-41. doi: 10.2147/DDDT.S82485. eCollection 2015.
Pharmacogenetics is the study of genetic polymorphisms affecting responses to drug therapy. The common rs7903146 (C>T) polymorphism of the TCF7L2 gene has recently been associated with type 2 diabetes (T2D). In this study, prevalence of the rs7903146 (C>T) polymorphism in the TCF7L2 gene for prediction of T2D risk was examined in an Iranian population of different ethnicities.
The prevalence of rs7903146 (C>T) and the predicted phenotypes, including extensive metabolizers, intermediate metabolizers, and poor metabolizers were investigated in blood samples of 300 unrelated healthy individuals in an Iranian population, including Fars, Turk, Lure, and Kurd, using polymerase chain reaction restriction fragment length polymorphism and direct genomic DNA sequencing.
The homozygous wild-type (C/C), heterozygous (C/T), and homozygous (T/T) allelic frequencies of rs7903146 (C>T) in the TCF7L2 gene were 29% (extensive metabolizers), 66.34% (intermediate metabolizers), and 4.66% (poor metabolizers), respectively. The C/C, C/T, and T/T genotypic frequencies of the rs7903146 (C>T) allele were significantly different (P<0.01) among Iranians of different ethnicities. The frequency of the homozygous T/T variant of the rs7903146 (C>T) allele was significantly low in the Lure (P<0.01) and high in the Fars (P<0.001) ethnicities. Additionally, the frequency of the T/T variant of the rs7903146 (C>T) allele in the South of Iran was the highest (P<0.04), while the East of Iran had the lowest frequency (P<0.01).
The prediction of rs7903146 (C>T) is required in drug research and routine treatment, where the information would be helpful for clinicians to optimize therapy and adverse drug reactions and predict drug response in individuals at risk of T2D.
药物遗传学是研究影响药物治疗反应的基因多态性。TCF7L2基因常见的rs7903146(C>T)多态性最近与2型糖尿病(T2D)相关。在本研究中,我们在不同种族的伊朗人群中检测了TCF7L2基因rs7903146(C>T)多态性预测T2D风险的患病率。
我们使用聚合酶链反应-限制性片段长度多态性和直接基因组DNA测序技术,在包括法尔斯人、土耳其人、卢尔人、库尔德人在内的300名无亲缘关系的伊朗健康个体的血液样本中,研究了rs7903146(C>T)的患病率以及预测的表型,包括快代谢者、中代谢者和慢代谢者。
TCF7L2基因rs7903146(C>T)的纯合野生型(C/C)、杂合型(C/T)和纯合型(T/T)等位基因频率分别为29%(快代谢者)、66.34%(中代谢者)和4.66%(慢代谢者)。rs7903146(C>T)等位基因的C/C、C/T和T/T基因型频率在不同种族的伊朗人中存在显著差异(P<0.01)。rs7903146(C>T)等位基因的纯合T/T变异在卢尔人中频率显著较低(P<0.01),在法尔斯人中频率显著较高(P<0.001)。此外,rs7903146(C>T)等位基因的T/T变异在伊朗南部频率最高(P<0.04),而在伊朗东部频率最低(P<0.01)。
在药物研究和常规治疗中需要对rs7903146(C>T)进行预测,这些信息将有助于临床医生优化治疗和药物不良反应,并预测T2D风险个体的药物反应。