WNT信号通路中抑制基因WIF1与DKK1基因多态性与中国汉族人群结核易感性的相关性研究  

Correlation between the polymorphisms of inhibition genes WIF1 and DKK1 in WNT signaling pathway and the susceptibility to tuberculosis in Chinese Han population

作　　者：刘堂喻亨 王念[1] 宋佳佳 胡雪姣[1] 赵珍珍[1] 彭武[1] 白浩 吴茜 应斌武[1] LIU Tangyuheng;WANG Nian;SONG Jiajia;HU Xuejiao;ZHAO Zhenzhen;PENG Wu;BAI Hao;WU Qian;YING Binwu(Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China)

机构地区：[1]四川大学华西医院实验医学科,成都610041

出　　处：《华西医学》2018年第8期958-965,共8页West China Medical Journal

基　　金：国家自然科学基金(81472026;81672095);国家科技重大专项艾滋病和病毒性肝炎等重大传染病防治项目(2012ZX10004-901);四川省卫生和计划生育委员会科研课题(16ZD004)

摘　　要：目的初步探究WNT信号通路中关键抑制基因WIF1和DKK1多态性位点与结核易感性、临床特征及实验室指标的相关性。方法纳入四川大学华西医院2014年12月—2016年11月期间475例结核病患者和370例健康对照,采用高通量基因分型技术对WNT信号通路中WIF1基因rs58635985位点和DKK1基因rs11001548位点多态性进行分型检测,并收集受试者相关临床资料。应用χ2检验、logistic回归模型等统计学方法分析单核苷酸多态性位点的等位基因、基因型、遗传模型在两组之间的分布差异,以及其是否影响结核患者临床表征。结果 WIF1 rs58635985位点和DKK1 rs11001548位点的等位基因(P=0.275、0.949)、基因型(P=0.214、0.659)及遗传模型:加性模型(P=0.214、0.659)、显性模型(P=0.414、0.827)与隐性模型(P=0.227、0.658)的频率分布在结核病组与健康对照组比较中差异无统计学意义。亚组分析显示:rs58635985和rs11001548等位基因和基因型分布差异无统计学意义(肺结核组vs.健康对照组:P>0.05;肺结核组vs.肺外结核组:P>0.05)。rs58635985位点和rs11001548位点在结核病相关临床特征(发热、盗汗、乏力等)以及实验室指标(血常规、红细胞沉降率、TB-DNA等)分析中差异无统计学意义(P>0.05)。结论未发现WIF1基因rs58635985位点和DKK1基因rs11001548位点与中国西部地区汉族人群结核病遗传易感性、临床特征及实验室指标有关联,后续仍需扩大样本量在不同人群中进行验证分析。Objective To explore the relationships between the polymorphisms of inhibitor genes WIF1 and DKK1 in WNT signaling pathway and susceptibility to tuberculosis, clinical characteristics and laboratory indexes.Methods From December 2014 to November 2016, 475 tuberculosis patients and 370 healthy controls of West China Hospital of Sichuan University were enrolled in the study, and the clinical data of the subjects were collected. Highthroughput genotyping technique was used to detect the polymorphisms of WIF1 rs58635985 and DKK1 rs11001548 in WNT signaling pathway. The allele frequency distribution, genotype, genetic model, clinical features and laboratory indexes of two single nucleotide polymorphisms were analyzed by χ2 test and logistic regression analysis. Results There was no significant difference in the allele frequency distribution（P=0.275, 0.949）, genotype（P=0.214, 0.659） or genetic models： additive model（P=0.214, 0.659）, dominant model（P=0.414, 0.827）, recessive model（P=0.227, 0.658） of rs58635985 and rs11001548 between the tuberculosis group and the healthy control group. Subgroup analysis showed no significant difference in allele and genotype distribution between rs58635985 and rs11001548（pulmonary tuberculosis group vs. healthy control group： P〈0.05; pulmonary tuberculosis group vs. extra-pulmonary tuberculosis group： P〈0.05）.There was no significant difference in the clinical features（fever, night sweat, fatigue, etc.） or laboratory indexes（complete blood count, erythrocyte sedimentation rate, TB-DNA, etc.）（P〈0.05）. Conclusions There is no association between rs58635985 of WIF1 gene or rs11001548 of DKK1 gene and genetic susceptibility, clinical characteristics and laboratory indexes in Han population in Western China. To expand the sample size for verification and analysis in different populations is necessary.

关 键 词：结核病 WNT信号通路 WIF1基因 DKK1基因 单核苷酸多态性 

分 类 号：R440[医药卫生—诊断学] R52[医药卫生—临床医学]