肾素-血管紧张素系统基因多态性与慢性心力衰竭的关系

Relationship Between Renin-angiotensin System Gene Ploymorphisms and Chronic Heart Failure

【目的】探讨中国南方汉族人群中,血管紧张素转换酶(ACE)及血管紧张素原(AGT)双基因多态性与慢性心力衰竭发病的关系。【方法】用聚合酶链反应及限制性片段长度多态性技术检测111例慢性心力衰竭患者和110例健康者的ACE基因I/D及AGT基因M235T的多态性。【结果】①慢性心力衰竭组DD基因型与D等位基因的频率均高于对照组。DD基因型0.468比0.227,P<0.01;D等位基因0.667比0.436,P<0.01。②AGT基因M235T多态性在慢性心力衰竭组及对照组的分布无统计学差异。③ACE及AGT双位点多态性联合分析显示慢性心力衰竭组DD+TT基因型频率显著高于对照组(0.351比0.117,P<0.01),与II+MM型者相比,具有该联合基因型者发生慢性心力衰竭的风险优势比(OR)为6.799,高于单基因分析的ACE-DD型者(OR=3.948)。【结论】ACE基因I/D多态性与中国南方汉族人群慢性心力衰竭的发生有关,ACE基因DD型可能是该地区慢性心力衰竭发病的遗传危险因素;单独AGT基因M235T多态性与慢性心力衰竭的发生似无明显关系,但AGT及ACE基因在慢性心力衰竭的发生中具有交互作用,DD型者若同时携带TT基因型,发生慢性心力衰竭的危险性增高。

[Objective] To investigate the relationship between angiotensin-converting enzyme （ACE） gene insertion/deletion （I/D） polymorphism and angiotensinogen （AGT） gene M235T polymorphism and the onset of chronic heart failure （CHF） on South Han Chinese population.[Methods] Polymerase chain reaction （PCR） and PCR combined with restrictive fragment length polymorphism （RFLP） were used to detect the I/D polymorphism of ACE gene and M235T variant of AGT gene in 111 patients with CHF and 110 heathy controls. The distribution of the genotypes and alleles of ACE and AGT of two groups were tested. [Results]① The genetype distribution of the ACE gene I/D polymorphism differed significantly in the patients with CHF and the contrast（χ^2=-20.175 ,P 〈 0.01 ）.The frequencies of DD genotype and D allele in the patients with CHF were higher than the latter （DD genotype：0.468 vs 0.227,χ^2= 14.158,P〈 0.01 ;D allele：0.667 vs 0.436,χ^2=-23.700,P〈 0.01）. ② The genotype distribution of the AGT gene M235T variant had no statistical difference between the experimental group and the contrast.③ In combined genotype analysis ,the genotype of ACE-DD＋AGT-TT was significantly higher in CHF patients （0.351 vs 0.117,χ^2=16.694,P〈 0.01 ）.The odds ratio estimated by the combined analysis of the ACE-DD and AGT-TT genotypes was 6.799 compared with Ⅱ＋MM combinations, and it was higher than that estimated separately from the ACE-DD（OR=3.948）.[Conclusion]The I/D polymorphism of ACE gene are associated with the occurrence of CHF in South Han Chinese population, and the genotype ACE-DD might be one of the genetic risk factors of CHF. The M235T polymorphism of AGT gene seems to have no correlation with the occurrence of CHF solely, but AGT and ACE may play an interaction role in the onset of CHF, and the DD genotype individual together with TT genotype may have more risk of CHF.