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目的观察终末期肾病(ESRD)患者L型钙离子通道α1C基因(CACNA1C)多态性和二氢吡啶类钙通道阻滞药降压疗效的关系。方法入选215例ESRD患者,用聚合酶链式反应(PCR)-直接测序法检测CACNA1C基因多态性,同时多元线性回归分析基因型与钙通道阻滞药降压疗效间的关系。结果 CACNA1C基因频率分布符合Hardy-Weinberg平衡分布。rs2238032 GT型携带者与TT型比较,血红蛋白(Hb)水平显著增加(117.53±20.89)vs(99.52±20.59)g·L~(-1)(P<0.01)。rs1051375高血压未控制组中AA型与GA、GG型比较,血肌酸酐显著降低(656.79±288.74)vs(937.8±295.15)vs(1113.2±433.44)μmol·L~(-1)(P<0.01)。rs2239128 CT型携带者与TT型和CC型比较,治疗有效者明显增加(P<0.01),CT型舒张压降幅(ΔDBP)表现出增加的趋势(P<0.05)。rs2238032基因型与血压的降幅相关(P<0.001),TT型收缩压降幅(ΔSBP)和ΔDBP明显高于GT型(P<0.01)。结论 CACNA1C基因多态性与钙通道阻滞药的降压疗效相关。
Objective To investigate the relationship between the LACC α1C gene (CACNA1C) polymorphism and the antihypertensive efficacy of dihydropyridine calcium channel blockers in patients with end-stage renal disease (ESRD). Methods A total of 215 patients with ESRD were enrolled in this study. The polymorphisms of CACNA1C gene were detected by polymerase chain reaction (PCR) - direct sequencing. Meanwhile, the relationship between genotypes and antihypertensive effects of calcium channel blockers was analyzed by multiple linear regression. Results The frequency distribution of CACNA1C gene conformed to the Hardy-Weinberg equilibrium distribution. Compared with TT genotype, rs2238032 GT carrier significantly increased the level of hemoglobin (117.53 ± 20.89) vs (99.52 ± 20.59) g · L -1 (P <0.01). Serum creatinine was significantly lower (656.79 ± 288.74) vs (937.8 ± 295.15) vs (1113.2 ± 433.44) μmol·L -1 (P <0.01) in the non-controlled hypertensive patients with AA and GA, ). Compared with TT and CC genotypes, rs2239128 CT type carriers showed a significant increase in effective treatment (P <0.01) and a decrease in CT diastolic blood pressure (ΔDBP) (P <0.05). The genotype of rs2238032 correlated with the decrease of blood pressure (P <0.001). The TT systolic pressure drop (ΔSBP) and ΔDBP were significantly higher than those of GT (P <0.01). Conclusion CACNA1C gene polymorphism is related to the antihypertensive effects of calcium channel blockers.