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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 the interaction between low-dose amlodipine and antihypertensive effect of body mass index (BMI) and L-type calcium ion channel α1C gene (CACNA1C) single nucleotide polymorphism (SNP) Methods The genotypes of CACNA1C SNPs rs1051375, rs2238032, rs2239050, rs2239128 in 181 patients with essential hypertension taking amlodipine as the main antihypertensive drug were genotyped by PCR direct sequencing. The interaction between BMI and SNP on antihypertensive efficacy was analyzed by multivariate analysis of variance and ORT Logistic regression. Results After adjusting for baseline blood pressure, age, sex, uric acid, triglyceride, and medication, the BMI and rs2238032G / T loci were correlated with the systolic pressure drop after treatment (B = -0.612, P = 0.044; B = 11.818, P = 0.037). The rs2238032G / T locus was also correlated with the decrease of diastolic blood pressure after treatment (B = 12.450, P = 0.001). Multivariate analysis of variance showed that there was an interaction between rs2238032G / T genotype and BMI (P <0.05), and the antihypertensive effect of amlodipine in TT genotype rs2238032G / T and normal BMI (<25kg / m2) Overweight patients carrying GT and GG genotypes. Logistic regression analysis also showed that the genotype of rs2238032G / T had an interaction with BMI (B = 0.212, P = 0.066). Conclusion The genotypes of rs2238032G / T at BMI and CACNA1C may interact with antihypertensive effects of low dose amlodipine.