华西医学

华西医学

WNT 信号通路中抑制基因 WIF1DKK1 基因多态性与中国汉族人群结核易感性的相关性研究

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目的 初步探究 WNT 信号通路中关键抑制基因 WIF1DKK1 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. High-throughput 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 groupvs. 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

Key words: Tuberculosis; WNT signaling pathway; WIF1 gene; DKK1 gene; Single nucleotide polymorphism

引用本文: 刘堂喻亨, 王念, 宋佳佳, 胡雪姣, 赵珍珍, 彭武, 白浩, 吴茜, 应斌武. WNT 信号通路中抑制基因 WIF1DKK1 基因多态性与中国汉族人群结核易感性的相关性研究 . 华西医学, 2018, 33(8): 958-965. doi: 10.7507/1002-0179.201807066 复制

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