目的探讨缺乏赖氨酸的丝氨蜃受/苏氨酸蛋白激酶1(WNK1)基因单核苷酸多态性与血管紧张素转换酶抑制剂(ACEI)降压疗效的相关性。方法选取新发的轻中度原发性高血压病患者121例,均来自北京市昌平地区的常住汉族人群。予以贝那普利口服治疗8周,对降压疗效进行评定。利用TaqManMGB等位基因分型试剂盒检测患者WNK1基因多态性rs880054和rs2301880的分布频率。结果患者rs880054位点和rs2301880位点不同基因型的降压疗效间差异有统计学意义(P〈0.05)。rs880054位点不同基因型的舒张压(DBP)降低幅度间差异有统计学意义(P〈0.05),收缩压(SBP)降低幅度间差异无统计学意义(P〉0.05);rs2301880位点不同基因型的DBP降低幅度间差异有统计学意义(P〈0.05),SBP降低幅度间差异无统计学意义(P〉0.05)。rs880054位点不同基因型与经ACEI治疗后DBP的降低幅度有关(R^2=0.167,P〈0.001);rs2301880位点不同基因型同样与治疗后DBP的降低幅度有关(R^2=0.080,P=0.003);未发现上述两位点与SBP降低幅度的相关性。结论WNK1基因单核苷酸多态性可能与ACEI的降压疗效有关。
Objective To investigate the correlation between the rs880054 and rs2301880 polymorphisms of the WNK1 gene and the blood pressure response to angiotensin - converting enzyme inhibitors (ACEI) in patients with essential hypertension. Methods A total 121 patients with mild to moderate essential hypertension, who are Han nationality from a district of Bei- jing, were recruited. Oral Benazepril was administered to the patients for 8 weeks. Genotyping was performed to identify the polymorphisms of the WNK1 gene. Results There was significant difference in antihyperactive effect between patients with rs880054 and rs2301880 polymorphisms of the WNK1 gene (P 〈0. 05 ). There was a significant difference between patients with rs880054 polymorphisms in reduction of diagnostic blood pressure (DBP) (P 〈 0. 05 ), but no significant difference in systolic blood pres- stire (SBP) ( P 〉 0. 05 ). There was a significant difference between patients with rs2301880 polymorphisms in reduction of DBP, but no significant difference in SBP ( P 〉 0. 05 ). After the treatment there were significant correlation between these two polymor- phisms and the reductions in DBP (rs880054 : R^2 = 0. 167, P 〈 0. 001 ; rs2301880 : R^2 = 0. 080, P = 0. 003), but no correlation was found in SBP. Conclusion The rs880054 and the rs2301880 polymorphisms of the WNK1 gene may be associated with the antihyperactive effect of ACEI in patients with essential hypertension.