体质量指数和L型钙离子通道α1C基因多态性对小剂量氨氯地平降压疗效的交互作用

Interaction between body mass index and genetic polymorphisms of L-type calcium channelα1Cgene in predicting the efficacy of low dose amlodipine in the treatment of essential hypertension

目的研究体质量指数(BMI)和L型钙离子通道α1C基因(CACNA1C)单核苷酸多态性(SNP)对小剂量氨氯地平降压疗效的交互作用。方法采用PCR直接测序法对服用以氨氯地平为主要降压药物的原发性高血压患者181例的CACNA1C基因SNPrs1051375、rs2238032、rs2239050、rs2239128等位点进行基因分型。采用多因素方差分析和有序Logistic回归方法分析BMI和SNP对降压疗效的交互作用。结果经多元线性回归方法调整基线血压、年龄、性别、尿酸、三酰甘油、药物等因素后,BMI和rs2238032G/T位点与用药后收缩压降幅均相关(B=-0.612,P=0.044;B=11.818,P=0.037),rs2238032G/T位点与用药后舒张压降幅亦相关(B=12.450,P=0.001)。多因素方差分析显示rs2238032G/T位点基因型与BMI存在交互作用(P<0.05),携带rs2238032G/T位点TT基因型和BMI正常(<25kg/m2)患者对氨氯地平的降压疗效高于携带GT和GG基因型的超重患者。有序Logistic回归分析亦显示出rs2238032G/T位点GT基因型与BMI存在交互作用的趋势(B=0.212,P=0.066)。结论 BMI和CACNA1C基因rs2238032G/T位点基因型对小剂量氨氯地平的降压疗效可能存在交互作用。

Objective To study interaction effects between body mass index（BMI）and genetic polymorphisms of L-type calcium channelα1Cgene（CACNA1C）on predicting the efficacy of amlodipine in the treatment of hypertension. Methods A pharmacogenetic analysis was performed on 181Chinese individuals with essential hypertension who were treated with a low dose amlodipine based antihypertensive drugs. SNPs rs1051375,rs2238032, rs2239050,rs2239128 in CACNA1Cgene were genotyped using PCR and direct sequencing method. Multiple linear regression was used to association analysis between BMI（genotypes）and efficacy of amlodipine. Multivariate analysis of variance and ordinal logistic regression was used to interaction effects analysis between BMI and genotypes on efficacy of amlodipine. Results After adjustment of the influence of confounding factors including basic blood pressure,age,gender,uric acid,triglyeride and drug,both BMI and genotypes of rs2238032G/T in CACNA1C were associated with systolic BP reduction after treatments（B=-0.612,P=0.044;B=11.818,P=0.037,respectively）,and rs2238032 G/T also was related to diastolic BP reduction（B=12.450,P=0.001）. Multivariate analysis of variance showed a significant interaction effect between BMI and genotypes of rs2238032 G/T on efficacy of amlodipine（P0.05）. The carriers of the TT genotype with a normal BMI had a better treatment response to amlodipine contrasted to the carriers of other genotypes with abnormal BMI. And ordinal Logistic regression showed a similar trend in interaction effect between BMI and rs2238032 G/T genotype GT on efficacy of amlodipine（B=0.212,P=0.066）. Conclusion BMI and SNP rs2238032 in CACNA1Cgene may have a interaction effect on efficacy of amlodipine in the treatment of essential hypertension.