血管紧张素Ⅱ1型受体基因多态性与心力衰竭预后的相关性研究

目的评价血管紧张素Ⅱ1型受体(AngiotensinⅡtype 1 receptor,AT1R)基因1166位点A/C基因多态性对心力衰竭预后的影响。方法432例患者来源于美国匹兹堡大学医疗中心的心血管事件基因危险性评价研究组,均有收缩功能障碍性心力衰竭〔射血分数(EF)<0.45〕。入选时间为1996年4月至2001年1月,前瞻性随访患者(26.43±18.19)月,随访终点是死亡或心脏移植。用聚合酶链式反应(PCR)方法鉴定AT1R基因A1166C位点基因型,分析AT1R A1166C基因多态性对心力衰竭患者生存率的影响。结果AT1R纯合子CC型8.6%,纯合子AA型50.0%,杂合子AC型41.4%。三组基因型在年龄、性别、种族、病因、血压和治疗方面无显著性差异,而在NYHA心功能分级的比例有显著性差异,AT1R C等位基因与较低心功能分级密切相关(P=0.04),但随访三组基因型的三年生存率并无显著性差异。结论在本组收缩功能障碍性心力衰竭患者中,AT1R C等位基因仅与较低心功能分级密切相关,并不影响未行心脏移植心力衰竭患者的预后。

Influence of angiotensin Ⅱ type 1 receptor polymorphism on clinical outcomes in patients with heart failure

Object To evaluate the impact of the angiotensin Ⅱ type 1 receptor(AT1R) A1166C polymorphism on heart failure phenotype and outcome.Methods 432 subjects with heart failure due to systolic dysfunction(EF<0.45) were enrolled between April 1996 and January 2001 in the GRACE study(Genetic Risk Assessment of Cardiac Events),a single center study at the University of Pittsburgh Medical Center.Demographic information,New York Heart Association Class,previous cardiovascular evaluation,and medical therapy were recorded at entry,and subjects were followed prospectively to an end point of either death or heart transplantation.The median follows up time for all patients were 26.43 ± 18.19 months.Genomic DNA was extracted from peripheral blood, and the AT1R A1166C polymorphism genotypes were determined by polymerase chain reaction(PCR).Continuous baseline characteristics and outcomes were analyzed by A1166C genotype subset.Results For AT1R A1166C genotyping,8.6% of patients as homozygous for the C allele,(50.0%) homozygous for the A allele,and 41.4% as heterozygous(AC).There were no significant difference in age,sex,race,cause,blood pressure and therapy among the 3-genotype subgroups;The AT1R 1166 C allele was associated with lower NYHA Class(AA/AC/CC= 2.62± 0.61/ 2.51 ± 0.63/ 2.43 ± 0.69,P= 0.04).The presence of the AT1 R 1166 C gene was not associated with poor transplant-free survival(1 year percent survival AA/AC/CC=79/79/86,2-year=67/70/71,3-year=58/59//61,P=0.36).Conclusion In this study with heart failure caused by systolic dysfunction,the AT1R C allele is associated with lower NYHA class,but did not affect transplant free survival.