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目的探讨中国西部地区藏族人群Wnt信号通路相关基因多态性位点与结核病易感性的关系。方法采用MassARRAY质谱分析法对488例藏族结核病患者(病例组)和454例藏族健康对照(对照组)进行Wnt信号通路中5个基因单核苷酸多态性(SNP)检测,分别为CTNNB1基因rs4135385位点、DKK1基因rs11001553位点、WIF1基因rs56900803位点、SFRP1基因rs7832767位点和AXIN2基因rs11079571位点。计算目标SNPs的基因型及等位基因频率的分布,并对差异有统计学意义的突变位点进行遗传模型分析(共显性、显性、隐性模型)。同时,比较目标SNPs在藏族与汉族两个群体中的多态性差异。结果 5个SNPs位点在病例组与对照组的频率分布均符合Hardy-Weinberg平衡。SFRP1rs7832767在病例组和对照组中的基因型和等位基因频率分布差异有统计学意义(P=0.004,0.002)。相较于野生型等位基因C,突变等位基因T可能增加藏族人群患结核病的风险〔比值比(OR)=1.260,95%可信区间(95%CI):1.086~1.471,P=0.002〕。该位点的共显性遗传模型TT/CC,显性遗传模型TC+TT/CC及隐性遗传模型TT/CC+TT都显示出与高结核病发病风险相关(P值分别为0.004,0.030、0.002,OR值分别为2.31、1.33、2.15)。其余4个SNPs位点的基因型频率与等位基因频率分布在两组中相似,差异无统计学意义(P均>0.05)。比较汉族、藏族结核人群发现:CTNNB1基因rs4135385位点的基因型频率和等位基因频率在两组人群中的分布不一致,差异有统计学意义(P=0.035,0.021),其余4个SNPs位点在两民族间的分布差异无统计学意义(P均>0.05)。结论 Wnt信号通路SFRP1基因多态性与中国西部地区藏族人群结核病的发生相关,SFRP1基因可能属于结核病的易感基因。CTNNB1基因多态性提示藏、汉族人群具有不同的遗传背景。
Objective To investigate the relationship between Wnt signaling pathway-related gene polymorphism and susceptibility to tuberculosis in Tibetan population in western China. Methods 488 Tibetan patients with tuberculosis (case group) and 454 Tibetan healthy controls (control group) were tested for the single nucleotide polymorphism (SNP) of 5 genes in Wnt signaling pathway by using MassARRAY mass spectrometry. They were CTNNB1 gene rs4135385, rs11001553 of DKK1, rs56900803 of WIF1, rs7832767 of SFRP1 and rs11079571 of AXIN2. The distribution of genotype and allele frequency of target SNPs was calculated, and the genetic model analysis was made for the mutation sites with statistical difference (co-dominant, dominant and recessive models). At the same time, the polymorphism of target SNPs in Tibetan and Han populations was compared. Results The frequency distribution of 5 SNPs in case group and control group all accorded with Hardy-Weinberg equilibrium. SFRP1rs7832767 in the case group and control group genotype and allele frequency distribution difference was statistically significant (P = 0.004,0.002). Mutational allele T may increase the risk of tuberculosis among Tibetan populations compared to wild-type allele C (odds ratio = 1.260, 95% confidence interval (95% CI): 1.086-1.471, P = 0.002 ]. The co-dominant genetic model TT / CC, dominant genetic model TC + TT / CC and recessive genetic model TT / CC + TT showed high risk of developing tuberculosis (P = 0.004,0.030, 0.002, OR values were 2.31, 1.33, 2.15 respectively). The other four SNPs loci genotype frequency and allele frequency distribution in the two groups were similar, the difference was not statistically significant (P all> 0.05). Comparing Han and Tibetan TB population, we found that genotype frequency and allele frequency of rs4135385 in CTNNB1 gene were not consistent among the two groups (P = 0.035,0.021), and the other four SNPs There was no significant difference between the two ethnic groups (P> 0.05). Conclusion The SFRP1 gene polymorphism of Wnt signaling pathway is associated with the occurrence of tuberculosis in Tibetan population in Western China. SFRP1 gene may be a susceptible gene to tuberculosis. The CTNNB1 gene polymorphism suggests that the Tibetan and Han populations have different genetic backgrounds.