L型钙离子通道α1C亚基基因多态性与钙通道阻滞药降压疗效的关系

Relationship of the calcium channel voltage- dependent L type,alpha 1C subunit gene polymorphism and efficacy of calcium channel blockers

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 evaluated the association of calcium channel voltage - dependent L type, alpha 1C subunit gene （ CACNAI C） polymor- phism with the effectiveness of calcium channel blockers （CCB） therapy in endstage renal disease （ESRD） patients. Methods The distribution of CACNA1C polymorphism 215 ESRD patients was investigated via the polymeras chain reaction and bidirectional sequencing. Multiple linear regression was used to association analysis between polymorphisms and efficacy of CCB. Results The CACNA1C genotype distributions were in Hardy - Weinberg equilibrium. The patients with rs2238032 genotype who carried the GT allele had higher haemoglobin levels when compared to carriers of TT genotypes （ 117.53 ±20. 89） vs （99.52 ±20.59） g· L-1 （P 〈0.01）. The patients with rs1051375 genotype who carried the AA allele had lower serume ereatinine levels when compared to carriers of GA and GG genotypes （656.79 ± 288.74） vs （937.8 ± 295.15） vs （ 1113.2 ±433.44）umol L-1 （P 〈0.01 ）. Compared to carriers of Tr and CC genotypes, CT genotypes had high trend of ADBP level （ P 〈 0. 05 ）. Multivariate analysis of variance showed a significant effect of rs2238032 genotypes on the efficacy of CCB. The carriers with the Tr genotype had a better treatment response to CCB compared to the GT carriers. Conclusion Our results suggest that the CACNA1C polymorphism may be associated with the efficacy of CCB therapy in ESRD patients.