【作者】 华荣；

【导师】 徐志云； 黄盛东；

【作者基本信息】 第二军医大学 ， 外科学， 2009， 博士

【摘要】 目的:研究肿瘤坏死因子α诱导蛋白3(tumor necrosis factor-induced protein 3,TNFAIP3)和肿瘤坏死因子受体相关因子1(TNF receptor associated factor 1,TRAF1)基因单核苷酸多态性(single nucleotide polymorphism,SNP)与中国汉族人风湿性心脏病(rheumatic heart disease,RHD)的关联。方法:关联研究采用1:2匹配病例-对照设计(239例RHD患者和478例对照)。遗传易感性位点选择采用tSNP(tagging single nucleotide polymorphisms,tSNP)策略。TNFAIP3基因共选择了3个tSNP, TRAF1基因共选择了2个tSNP。各位点基因分型检测采用SNPstream技术。结果:所有SNPs的基因型频率在病例组及对照组均符合Hardy-Weinberg平衡。两个基因所有tSNPs之间的连锁不平衡程度都较弱。位于TNFAIP3基因第5内含子上的SNP rs582757位点基因型和等位基因型频率在病例组和对照组之间都有显著差异,P值分别为0.001249和0.000374。在rs582757位点C等位基因的加性模型时,每增加一个拷贝的C等位基因,RHD风险是增加前的0.574倍(95%CI 0.42-0.78,P=0.00037);在rs582757位点C等位基因的显性模型时,携带CC/TC基因型的个体RHD风险是TT基因型个体的0.535倍(95%CI 0.38-0.75,P=0.000328)。在调整年龄、性别、吸烟史和饮酒史后,显著性仍然存在(加性和显性模型调整后的P值分别为0.007和0.009)。未发现其余各SNPs与RHD显著相关。结论:TNFAIP3基因的SNP rs582757的多态性与RHD发病相关,其C等位基因可能是中国汉族人RHD的保护因素。目的:研究可结晶片段受体样因子3(Fc receptor-like 3,FcRL3)、蛋白酪氨酸磷酸酶非受体型22(protein tyrosine phosphatase nonreceptortype 22,PTPN22)和C5(complement component 5)基因单核苷酸多态性与中国汉族人风湿性心脏病的关联。方法:关联研究采用1:2匹配病例-对照设计(239例RHD患者和478例对照)。遗传易感性位点选择采用tSNP策略,FcRL3基因选择了2个tSNP,PTPN22基因选择了2个tSNP, C5基因共选择了7个tSNP。各位点基因分型检测采用SNPstream技术。结果:所有SNPs的基因型频率在病例组及对照组均符合Hardy-Weinberg平衡。两个基因所有tSNPs之间的连锁不平衡程度都较弱。位于FcRL3基因第15外显子上的SNP rs6691569的基因型和等位基因型频率在病例组和对照组之间都有显著差异,P值分别为0.000213和0.0000542。在rs6691569位点C等位基因的加性模型时,每增加一个拷贝的C等位基因,RHD风险是增加前的0.537倍(95%CI 0.34-0.73,P=0.0000625);在rs6691569位点C等位基因的显性模型时,携带CC/TC基因型的个体RHD风险是TT基因型个体的0.496倍(95%CI 0.35-0.70,P=0.000006)。在调整年龄、性别、吸烟史和饮酒史后,显著性仍然存在(加性和显性模型调整后的P值分别为0.017和0.018)。未发现其余各SNPs与RHD显著相关。结论:FcRL3基因的SNP rs6691569的多态性与RHD发病相关,其C等位基因可能是中国汉族人RHD的保护因素。更多还原

【Abstract】 Objectives: To investigate the association between tumor necrosis factor-induced protein 3 (TNFAIP3) gene and tumor necrosis factor receptor associated factors 1 (TRAF1) gene and rheumatic heart disease (RHD) in Chinese Hans.Design and methods: In a pair-matched, hospital-based case control study (239 versus 478) conducted in Chinese Hans, we genotyped four tagging single nucleotide polymorphisms (tSNPs) in the TNFAIP3 gene and two polymorphisms in the TRAF1 gene and determined their association with RHD.Results: We observed that rs582757 in intron 5 of the TNFAIP3 gene was significantly associated with RHD in Chinese Hans. There was significant difference of the genotype frequency and the allele frequency in RHD patients compared with those of control subjects. (p=0.001249 and 0.000374, respectively) The C allele was associated with a reduced risk of RHD with the per-allele risk of 0.574 (95%CI 0.42-0.78, P=0.00037) under a additive model. The CC/TC genotype was associated with a reuced risk of 0.535 (95%CI 0.38-0.75, P=0.000328), compared with TT genotypes, assuming a dorminant model. The risk of rs582757 remained significant after adjusting for covariates of age,gender, smoking and alchohol drinking. ( p=0.007 and 0.009, respectively)Conclusions: This study demonstrates for the first time that polymorphisms rs582757 in TNFAIP3 gene may influence the risk of RHD in Chinese Hans. Objectives: To investigate the association between Fc receptor-like 3 (FcRL3) gene,protein tyrosine phosphatase nonreceptortype 22 (PTPN22) gene and complement component 5 (C5) gene and rheumatic heart disease (RHD) in Chinese Hans.Design and methods: In a pair-matched, hospital-based case control study (239 versus 478) conducted in Chinese Hans. We genotyped two tagging single nucleotide polymorphisms (tSNPs) in the FcRL3 gene, two in the PTPN22 gene and seven in the C5 gene, and determined their association with RHD.Results: We observed that rs6691569 in exon 15 of the FcRL3 gene was significantly associated with RHD in Chinese Hans. There was significant difference of the genotype frequency and the allele frequency in RHD patients compared with those of control subjects. ( p=0.000213 and 0.0000542, respectively) The C allele was associated with a reduced risk of RHD with the per-allele risk of 0.537 (95%CI 0.34-0.73, P=0.0000625) under a additive model. The CC/TC genotype was associated with a reuced risk of 0.496 (95%CI 0.35-0.70, P=0.000006), compared with TT genotypes, assuming a dorminant model. The risk of rs6691569 remained significant after adjusting for covariates of age,gender, smoking and alchohol drinking. ( p=0.017 and 0.018, respectively)Conclusions: This study demonstrates for the first time that polymorphisms rs6691569 in FCRL3 gene may influence the risk of RHD in Chinese Hans.更多还原