西安地区306例原发性高血压患者与降压药物相关的基因多态性分布特征分析

Analysis of the Distribution Characteristics of Gene Polymorphism Related to Antihypertensive Drugs in 306 Patients with Essential Hypertension in Xi’an Area

目的分析西安地区原发性高血压(essential hypertension,EH)人群中9个高血压药物相关基因的多态性分布特征,为个性化治疗提供客观依据。方法选择2022年1月~2023年12月,在武警陕西省总队医院就诊的306例EH患者作为研究对象,采用PCR-熔解曲线法检测9个高血压药物相关基因的多态性,分析其基因型及等位基因位点分布频率,并比较不同性别、年龄、高血压分级组患者基因多态性的相关情况。结果在306例患者中,各基因分布频率符合Hardy Weinberg平衡(χ^(2)=0.153~2.941,均P>0.05)。各基因位点突变率:SLCO1B1 c.388A>G为77.29%,ADRB1 c.1165G>C为73.20%,MTHFR C677T为56.54%,ADDl c.1378G>T为48.37%,CYP2D6 c.100C>T为50.82%,ACE I/D为35.13%,CYP3A5 c.806-4288C>T为29.41%,SLCO1B1 c.521T>C为11.76%,AGTR1 c.1166A>C为7.68%,CYP2C9 c.1075A>C为3.43%,CYP2C9 c.403C>T无突变。在不同性别患者之间比较发现:男性组SLCO1B1c.388A>G基因型及等位基因突变率高于女性组(χ^(2)=5.221,8.237);女性组CYP2D6 c.100C>T基因型及等位基因突变率高于男性组(χ^(2)=5.093,9.661);男性组ACE I/D等位基因型突变率高于女性组(χ^(2)=6.118,8.022),差异具有统计学意义(均P<0.05)。老年组和中青年组间比较发现,中青年组CYP2C9 c.1075A>C,SLCO1B1 c.388A>G,CYP2D6c.100C>T基因型与等位基因突变率均高于老年组,差异具有统计学意义(χ^(2)=11.683,10.243;9.003,9.803;10.617,9.931,均P<0.05)。其余基因型及等位基因在不同性别及年龄组间比较,差异无统计学意义(χ^(2)=1.321~7.733,均P>0.05)。不同高血压分级组之间各基因型及等位基因突变频率比较,差异无统计学意义(χ^(2)=1.031~5.198,均P>0.05)。结论西安地区抗高血压药物相关基因多态性分布与EH患者性别、年龄有关,降压药物基因型检测对于EH患者的个性化用药治疗具有重要指导意义。

Objective To analyze the distribution characteristics of 9 hypertension drug related gene polymorphisms in the population of essential hypertension(EH)in Xi’an area,providing an objective basis for personalized treatment.Methods A total of 306 EH patients who visited the Shaanxi Provincial Armed Police Force Hospital from January 2022 to December 2023 were selected as the research subjects.The PCR melting curve method was used to detect 9 hypertension drug related gene polymorphisms,their genotype and allele distribution frequency were analyzed,and the correlations of gene polymorphism among patients of different genders,ages,and hypertension grading groups were compared.Results Among 306 patients,the distribution frequencies of each gene were consistent with Hardy Weinberg equilibrium(χ^(2)=0.153~2.941,all P>0.05).Mutation rates of various gene were as follows:SLCO1B1 c.388A>G,ADRB1 c.1165G>C,MTHFR C677T,ADDl c.1378G>T,CYP2D6 c.100C>T,ACE I/D,CYP3A5 c.806-4288C>T,SLCO1B1 c.521T>C,AGTR1 c.1166A>C and CYP2C9 c.1075A>C were 77.29%,73.20%,56.54%,48.37%,50.82%,35.13%,29.41%,11.76%,7.68%and 3.43%,respectively,and CYP2C9 c.403C>T had no mutation.Comparing with patients of different genders,the mutation rate of SLCO1B1 c.388A>G genotype and allele mutations in male group were higher than those in the female group(χ^(2)=5.221,8.237),the mutation rate of CYP2D6 c.100C>T genotype and allele in the female group were higher than those in the male group(χ^(2)=5.093,9.661),the mutation rate of ACE I/D allele in the male group was higher than that in the female group(χ^(2)=6.118,8.032),with significant differences(all P<0.05).The mutation rates of CYP2C9 c.1075A>C,SLCO1B1 c.388A>G,CYP2D6 c.100C>T genotypes and alleles in the middle-aged and young age group were higher than those in the elderly group,and the differences were statistically significant(χ^(2)=11.683,10.243,9.003,9.803,10.617,9.931,all P<0.05).There was no significant difference in the comparison of other genotypes and alleles among different gender and age groups and in the frequency of genotype and allele mutations among different hypertension grading groups(χ^(2)=1.321~7.733,1.031~5.198,all P>0.05).Conclusion The distribution of gene polymorphisms related to antihypertensive drugs in the Xi’an area was related to the gender and age of EH patients.Thus,the genotype testing of antihypertensive drugs may have important guiding significance for personalized medication treatment of EH patients.