IFNA8基因单核苷酸多态性与我国汉族人群结核分枝杆菌易感性的关联分析

Study on the relationship between single nucleotide polymorphisms of IFNA8 gene and susceptibility to Mycobacterium tuberculosis in Han Chinese

目的 探讨我国汉族人群IFNA8基因单核苷酸多态性（single nucleotide polymorphisms,SNPs）与结核分枝杆菌易感性的关系.方法 收集2010年1月至2011年12月期间深圳市第三人民医院收治的结核病患者资料,采用病例对照研究方法,应用MassARRAY飞行时间质谱生物芯片技术,分成检测结核病组（1533例）和对照组（1445名）IFNA8基因SNPs（rs1330322、rs10964982、rs4978116）的基因型,计算各SNP位点等位基因频率（allele frequency,AF）,应用“四格表”x2检验比较两组人群中候选SNP位点等位基因频率的差别,以P＜0.05为差异有统计学意义,并计算相应的比值比（odds ratio,OR）和95％置信区间（95％CI）.结果 （1）rs1330322位点A等位基因频率在结核病组、对照组中分别为30.5％（936/3066）、27.8％（804/2890）,差异有统计学意义（x2=5.277,OR=1.140,95％CI=1.019～1.275,P=0.022）.rs10964982和rs4978116位点的次要等位基因频率在结核病组中分别为17.0％（520/3066）和28.8％（882/3066）,在对照组中分别为17.0％（491/2890）和28.6％（826/2890）,两组间差异无统计学意义（x2值分别为0.001、0.025,P值分别为0.976、0.874）.（2）根据性别分层发现,结核病组女性患者中,rs1330322位点等位基因A频率为30.8％（330/1072）,对照组等位基因A频率为26.6％（300/1126）,两组间差异有统计学意义（x2=4.605,OR=1.225,95％CI=1.018～1.474,P=0.032）.男性结核病组、对照组患者等位基因A频率分别为30.4％（606/1994）、28.6％（504/1764）,两组间差异无统计学意义（x2=1.489,OR=1.091,95％CI=0.948～1.256,P=0.222）.（3）对女性患者进一步进行年龄分层发现,对于rs1330322位点,≤25岁结核病组、对照组A等位基因频率分别为33.8％（111/328）、25.2％（112/444）,两组间差异有统计学意义（x2=6.818,OR=1.516,95％CI=1.108～2.074,P=0.009）.而＞25岁人群A等位基因在两组人群中差异无统计学意义（x2=0.610,OR=1.096,95％CI=0.871～1.380,P=0.435）.结论 SNP位点rs1330322与结核分枝杆菌易感性密切相关,rs1330322位点基因型在女性、年龄≤25岁组人群具有更高的结核病患病风险预测价值.

Objective To study the association between single nucleotide polymorphisms （SNP） of IFNA8 gene and the susceptibility to Mycobacterium tuberculosis in Han Chinese.Methods From January 2010 to Decem ber 2011,clinical data of pulmonary tuberculosis patients was collected from Shenzhen Third People＇s Hospital.There were 1533 patients with tuberculosis as case group and 1445 volunteers as healthy controls.A case-control study was used in the research.SNPs of IFNA8 （rs1330322,rs10964982,rs4978116） were typed by a highthroughput sequenom genotyping platform.The allele frequency （AF）,odds ratio （OR） and 95％ confidence interval （95％CI） were calculated between case group and control group by using Chi square test,P＜0.05 was considered to be significant.Results （1） The frequencies of allele A in the genetic locus rs1330322 were 30.5％（936/3066） in tuberculosis patients （TB） group and 27.8％ （804/2890） in healthy control （HC） group.There were statistical differences between two groups（x2 =5.277,OR =1.140,95％CI=1.019-1.275,P =0.022）.The minor allele frequencies of rs10964982 and rs4978116 of TB group were 17.0％ （520/3066） and 28.8％（882/3066）,respectively.And the minor allele frequencies of rs10964982 and rs4978116 of HC group were 17.0％ （491/2890） and 28.6 ％ （826/2890）,respectively.The minor allele frequencies of rs10964982 and rs4978116 were no significant differences between two groups （x2=0.001 and 0.025,P =0.976 and 0.874）.（2） In sexual stratified analysis of rs1330322,the frequencies of allele A in female population of case group were 30.8％（330/1072）,and 26.6％（300/1126） in female of HC group.There were significant differences between two groups of female population （x2=4.605,OR=1.225,95％CI =1.018-1.474,P=0.032）.However,among male population,the frequencies of allele A were 30.4％（606/1994） and 28.6％ （504/1764） in TB group and HC group without significant differences statistically （x2 =1.489,OR=1.091,95％CI =0.948-1.256,P =0.222）.（3） The frequencies of allele A in female less than 25 years old were 33.8％（111/328）and 25.2％ （112/444）,respectively.There were significant differences between TB group and HC group （x2=6.818,OR =1.516,95％CI =1.108-2.074,P=0.009）.But the frequencies of allele A in female more than 25 years old were not significantly different between two groups （x2 =0.610,OR=1.096,95％CI=0.871-1.380,P=0.435）.Conclusion The genetic polymorphism of IFNA8 （rs1330322） is associated with TB,especially female population less than 25 years old.Allele A may be a risk factor for prediction of TB in female less than 25 years old.