扩张型心肌病心力衰竭患者npr1基因G1023C多态性对重组人B型利钠肽疗效的影响

The effects of the G1023C polymorphism in npr1 gene on the therapeutic efficacy of recombinant human B- type natriuretic peptide for dilated cardiomyopathy patients with heart failure

目的探讨扩张型心肌病(DCM)心力衰竭患者npr1基因(编码A型钠尿肽受体)的G1023C多态性对重组人B型利钠肽(rh BNP)疗效的影响。方法 168例扩张型心肌病心力衰竭患者在常规抗心力衰竭治疗的基础上给予rh BNP治疗。观察治疗前、后的临床特征、心功能状态、心脏彩超及血浆N末端B型利钠肽原(NTpro BNP)水平,并采用聚合酶链反应和DNA测序的方法检测患者npr1的G1023C基因型。结果本研究中检测的GG基因型和GC+CC基因型频率分别为80.4%和19.6%,符合Hardy-Weinberg定律(P>0.05);治疗前GC+CC组患者NT-pro BNP水平显著高于GG组(P<0.05),其他指标两组间比较差异无统计学意义(P>0.05);rh BNP治疗后,比较GG组和GC+CC组临床指标变化的差值发现,GG组的左室射血分数差值(△LVEF)比GC+CC组显著提高(P<0.01),且GG组的△NYAH分级和△NT-pro BNP值比GC+CC组下降明显(均P<0.05),其他指标差异无统计学意义(P>0.05)。结论 DCM心力衰竭患者npr1基因G1023C多态性与rh BNP疗效可能有关,GG基因型患者比携带突变基因C的患者对rh BNP更为敏感,改善心功能的疗效更加明显。

Objective To investigate the effects of the G1023C polymorphism in nprl gene （encoding natriuretie peptide receptor A） on the therapeutic efficacy of recombinant human B - type natriuretic peptide （rhBNP） for dilated cardiomyopathy （DCM） patients with heart failure. Methods A total of 168 DC^J patients with heart failure were sub- jected to rhBNP treatment on the basis of conventional therapy. Before and after rhBNP treatment, the changes of clinical features, heart function, echocardiography, and the level of plasma N - terminal B - type natriuretic peptide （ NT - proB- NP） were compared. Polymerase chain reaction and DNA sequencing methods were used to detect the G1023C genotype of nprl in patients. Results In this study, the genotype frequencies of GG and GC ＋ CC were 80. 4% and 19. 6% , respec- tively, obeying the Hardy - Weinberg＇s law （P 〉0. 05）. Before rhBNP treatment, NT - proBNP level in GC ＋ CC group was significantly higher than that in GG group （ P 〈 0. 05 ） , but with no significant difference in the other indicators （ P 〉 0. 05）. After rhBNP treatment, the change of left ventricular ejection fraction （ALVEF） in GG group was significantly increased compared to that in GC ＋ CC group （ P 〈 0. 05 ） ; and /k NYAH grade and ANT - proBNP level in GG group were significantly reduced compared to those in GC ＋ CC group （P 〈 O. 05 ）. There was no significant difference revealed in the other indicators （P 〉 0. 05 ）. Conclusion The G1023C polymorphism in nprl gene may be closely associated with the therapeutic efficacy of rhBNP for DCM patients with heart failure. Patients of GG genotype are more sensitive to rhBNP treatment than those carrying the mutant allele C, providing more signifieant improvement in heart function.