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分析 2 型糖尿病患者 CYP2C9*2、CYP2C19*2 和 CYP2D6*4 多态性。

Analysis of CYP2C9*2, CYP2C19*2, and CYP2D6*4 polymorphisms in patients with type 2 diabetes mellitus.

机构信息

Department for Biochemistry and Clinical Analysis, University of Sarajevo, Bosnia and Herzegovina.

出版信息

Bosn J Basic Med Sci. 2010 Nov;10(4):287-91. doi: 10.17305/bjbms.2010.2662.

Abstract

This is the first study performed in population from Bosnia & Herzegovina (BH), in which we analysed a significance of genetic variations in drug-metabolising enzyme, cytochrome P450 (CYP), in pathogenesis of Type 2 diabetes. We have determined allele frequencies for CYP2C92, CYP2C192, and CYP2D64 in diabetic patients and nondiabetic controls. Genomic DNA was extracted from blood samples collected from 37 diabetic and 44 nondiabetic subjects. A real-time polymerase chain reaction was used for the detection of specific CYP polymorphisms, with the application of the specific TaqMan® SNP genotyping tests (Applied Biosystems). Interestingly, results from this study have demonstrated that frequencies of CYP2C192 and CYP2D64 variants were in line, while frequency of CYP2C92 polymorphism seemed to be lower in this sample of BH population as compared to the Caucasians genotype data. Furthermore, no significant difference in allele frequencies for CYP2C92, CYP2C192, and CYP2D6*4 was demonstrated between diabetic and nondiabetic subjects. Thus, results form this study seem to indicate no relationship between CYP2C9, CYP2C19, and CYP2D6 genotype and diabetes susceptibility in Bosnian population. This in part may reflect a limited study population included in our study and would require larger cohorts to reveal potential relationships between analysed CYP genetic variants and diabetes risk. In addition, it would be pertinent to further explore possible effects of CYP genetic variations on therapeutic and adverse outcomes of oral antidiabetics, which might be the key in optimising therapy for individual patient with Type 2 diabetes.

摘要

这是在波斯尼亚和黑塞哥维那(波黑)人群中进行的第一项研究,我们分析了药物代谢酶细胞色素 P450(CYP)的遗传变异在 2 型糖尿病发病机制中的意义。我们已经确定了糖尿病患者和非糖尿病对照组中 CYP2C92、CYP2C192 和 CYP2D64 的等位基因频率。从 37 名糖尿病患者和 44 名非糖尿病对照者采集的血液样本中提取基因组 DNA。使用实时聚合酶链反应(PCR)检测特定 CYP 多态性,应用特定的 TaqMan®SNP 基因分型检测(Applied Biosystems)。有趣的是,这项研究的结果表明,CYP2C192 和 CYP2D64 变体的频率一致,而 CYP2C92 多态性的频率似乎低于波黑人群的白种人基因型数据。此外,糖尿病患者和非糖尿病患者 CYP2C92、CYP2C192 和 CYP2D6*4 的等位基因频率无显著差异。因此,这项研究的结果表明,CYP2C9、CYP2C19 和 CYP2D6 基因型与波斯尼亚人群的糖尿病易感性之间没有关系。这在一定程度上可能反映了我们研究中纳入的研究人群有限,需要更大的队列来揭示分析的 CYP 遗传变异与糖尿病风险之间的潜在关系。此外,进一步探讨 CYP 遗传变异对口服抗糖尿病药物治疗和不良结局的可能影响将是至关重要的,这可能是优化 2 型糖尿病患者个体化治疗的关键。

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