蚌埠地区高血压病人药物基因多态性的分布

孙思雨; 尚茂林

doi:10.13898/j.cnki.issn.1000-2200.2022.07.018

摘要:

目的探讨高血压病人降压药物代谢酶基因位点CYP2C9*3(1075A>C)、CYP2D6*10(100C>T)、CYP3A5*3(6986A>G)和药物作用靶点基因位点AGTR1(1166 A>C)、ACE (I/D)、ADRB1(1165G>C)、NPPA (2238T>C)的基因型分布频率。为安徽蚌埠地区高血压病人β受体阻滞剂、血管紧张素受体拮抗剂、血管紧张素转换酶抑制剂、钙离子拮抗剂、利尿剂五大类降压药物的个性化用药提供理论基础。

方法使用PCR熔解曲线法检测2020年1-12月住院的879例高血压病人的药物基因位点多态性, 对各基因位点的分型频率进行分析。

结果879例高血压病人AGTR1(1166A>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为88.74%、10.92%、0.34%;ADRB1(1165G>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为5.23%、35.38%、59.39%;ACE (I/D)基因位点的野生型、杂合突变型、纯合突变型的频率分别为40.73%、43.12%、16.15%;NPPA (2238T>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为98.63%、1.37%、0%;CYP2C9*3(1075A>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为91.81%、7.96%、0.23%;CYP2D6*10(100C>T)基因位点的野生型、杂合突变型、纯合突变型的频率分别为25.94%、45.73%、28.33%;CYP3A5*3(6986A>G)基因位点的野生型、杂合突变型、纯合突变型的频率分别为7.17%、39.70%、53.13%。其中, CYP2C9*3(1075A>C)基因位点基因型在男性与女性病人中的分布差异有统计学意义(P < 0.05)。CYP2C9*3等位基因多态性在男性和女性病人的分布差异有统计学意义(P < 0.05)。CYP2D6*10等位基因多态性在男性和女性病人的分布差异有统计学意义(P < 0.05)。

结论获得安徽蚌埠地区原发性高血压人群的高血压药物相关的基因多态性分布频率的数据, 为建立病人基因库提供了基础, 便于后期继续深入研究相关基因位点的多态性在临床中指导的合理用药。

Abstract:

ObjectiveTo investigate the gene locus of antihypertensive drug metabolizing enzymes CYP2C9*3(1075A>C), CYP2D6*10(100C>T), CYP3A5*3(6986A>G) and genotype distribution frequency of the drug target gene loci AGTR1(1166 A>C), ACE(I/D), ADRB1(1165G>C) and NPPA(2238T>C), to provide a theoretical basis for the personalized medication of five types of antihypertensive drugs including β-blocker, angiotensin receptor antagonist, angiotensin-converting enzyme inhibitor, calcium ion antagonist, and diuretics in hypertensive patients in Bengbu area of Anhui.

MethodsThe PCR melting curve method was used to detect the gene locus polymorphism of drug in 879 hypertensive patients hospitalized from January 2020 to December 2020, and the typing frequency of each gene locus was analyzed.

ResultsThe frequency of wild type, heterozygous mutant and homozygous mutant of AGTR1(1166A>C) gene locus in 879 hypertensive patients was 88.74%, 10.92% and 0.34%, respectively, which was 5.23%, 35.38% and 59.39% for ADRB1(1165G>C) gene locus, 40.73%, 43.12% and 16.15% for ACE(I/D) gene locus, 98.63 %, 1.37% and 0% for NPPA(2238T>C) gene locus, 91.81%, 7.96% and 0.23% for CYP2C9*3(1075A>C) gene locus, 25.94%, 45.73% and 28.33% for CYP2D6*10(100C>T) gene locus, and 7.17%, 39.70% and 53.13% for CYP3A5*3(6986A>G) gene locus.Among them, the distribution difference of genotype at CYP2C9*3(1075A>C) gene locus was statistically significant between male and female patients(P < 0.05), and the distribution difference of allele gene polymorphism of CYP2C9*3 and CYP2D6*10 was statistically significant between male and female patients(P < 0.05).

ConclusionsThe data on the distribution frequency of hypertensive drug-related gene polymorphisms in the primary hypertension population in Bengbu area of Anhui have been obtained, which provide a basis for the establishment of a patient gene pool, and facilitate further study on the polymorphisms of related gene locus in future to guide rational drug use in clinic.

蚌埠地区高血压病人药物基因多态性的分布

Distribution of gene polymorphism of drug in hypertensive patients in Bengbu area