血管紧张素转化酶基因多态性与系统性红斑狼疮相关性研究

目的探讨位于人类17号染色体长臂2区3带(17q23)上的血管紧张素转化酶(ACE)基因多态性G261T与系统性红斑狼疮(SLE)的关系。方法采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)方法检测人类17q23上的ACE基因多态性G261T,运用家系为基础的相关性检验(FBAT)方法,对119个中国汉族SLE患者家系(其中核心家系95个,119例患者,316名家系其他成员)ACE多态性位点(rs4303)进行等位基因和基因型分析。结果在119例SLE患者中：G、T等位基凶频率分别是44．8%和55．2%：基因型GG、GT和TT的频率分别是13．9%,62．0%,24．1%。FBAT单位点分析显示G261T多态性与SLE显著相关：附加模型(Z=2．877．P=0．004),显性模型(Z=2．557,P=0．011)以及隐性模型(Z= 2．202,P=0．028)。传递不平衡检验(TDT)和同胞传递不平衡检验(STDT)显示其中ACE-261T等位基因由杂合子父母优势传递给患病子女或者与正常同胞相比更容易传递给患者(X~2=11．66,P=0．001)。结论ACE基因是中国汉族人群SLE的易感基因；其中ACE-261T等位基因与SLE发病相关。

Association of angiotensin converting enzyme gene polymorphism with genetic susceptibility to systemic lupus erythematosus

Objective The aim of this study is to investigate the role of angiotensin-converting enzyme (ACE)gene susceptibility to systemic lupus erythematosus(SLE)by familial studies.Methods PCR-based re- striction fragment length polymorphism(RFLP)was applied to genotype single nucleotide polymorphism(SNP) G261T of the ACE gene.A total of 119 patients with SLE from 119 families were recruited.In addition,316 family members of these patients were also genotyped.A family-based association study was carried out to ex- plore the association between gene polymorphism and SLE.We studied the SNP encoding non-synonymous substitution in the ACE gene with respect to genetic susceptibility to SLE.Results Among 119 SLE patients. the frequency of ACEG261TG,T alleles was 44.8%.55.2% respectively,the frequency of ACEG261T GG,GT and TT genotypes was 13.9%,62.0%,24.1% respectively,Univariate(single-marker)family-based association test(FBAT)demonstrated that variant alleles at the SNP,rs4303,exon 5 of ACE gene were significantly asso- ciated with genetic susceptibility to SLE in Additive Model(Z=2.877,P=0.004),Dominant Model(Z=2.557, P=0.011).Recessive Model(Z=2.202,P=0.028).Transmission-disequilibrium test(TDT)and sib transmission -disequilibrium test(STDT)showed an excess of the allele of T from heterozygous parents to affected offspring or higher frequency of the allele of T in the patients than their normal siblings(X~2=11.66,P=0.001).Conclu- sion Our findings suggest that the ACE gene may he the susceptible gene to SLE in Chinese population,and the individuals carrying ACE-261T allele is significantly associated with susceptibility to SLE.