TLR2基因多态性与中国汉族儿童结核病易感性的关联研究

Association between Polymorphisms of Toll like receptor 2 and the suseptibility to tuberculosis in Chinese Han children

目的探讨TLR2基因5个SNP位点多态性与中国汉族儿童结核病(TB)易感性的关联。方法以2005年2月至2010年10月在北京儿童医院临床诊断和确诊的TB且排除其他肺部感染的病例作为TB组,并根据感染部位和严重程度分别分为肺TB亚组、肺外TB亚组和重症TB亚组、非重症TB亚组;以健康查体且除外TB的儿童作为对照组。应用高通量Mass ARRAY技术对于TLR2基因的5个SNP位点:rs3804099(等位基因C/T)、rs1898830(等位基因A/G)、rs7656411(等位基因G/T)、rs11935252(等位基因A/G)、rs7696323(等位基因C/T)行基因分型,比较5个SNP位点各基因型和等位基因频率在TB组和对照组的差异,同时采用显性遗传和隐性遗传模式分析各TB亚组与对照组基因型的差异。结果 TB组345例,平均年龄(5.6±4.7)岁,男219例;肺TB亚组151例(43.8%),肺外TB亚组194例;重症TB亚组155例(44.9%),非重症TB亚组190例。对照组385例,年龄(6.1±3.8)岁,男226例。Hardy-Weinberg检验提示TLR2基因的5个SNP位点在TB组和对照组的基因型分布均符合遗传平衡(P=0.154~0.992)。调整了年龄和性别因素后,rs3804099位点TC、CC型和C等位基因频率TB组和对照组比较,OR=0.929~1.071;rs1898830位点GA、GG型和G等位基因频率TB组和对照组比较,OR=1.100~1.411;rs7656411位点GT、TT型和T等位基因频率TB组和对照组比较,OR=0.812~1.110;rs11935252位点GA、GG型和A等位基因频率TB组和对照组比较,OR=0.497~1.189;rs7656323位点CT、CC型和C等位基因频率TB组和对照组比较,OR=0.888~1.034;,差异均无统计学意义(P均>0.05)。5个SNP按照显性和隐性遗传模式分析,各基因型TB组和对照组间差异均无统计学意义(P均>0.05)。2TLR2基因的5个SNP位点在显性或隐性遗传模式下,基因型频率在肺TB亚组、肺外TB亚组和对照组比较,OR=0.737~1.326;重症TB亚组、非重症TB亚组和对照组比较,OR=0.675~1.248;差异均无统计学意义(P均>0.05)。3TLR2基因5个SNP位点在各染色体之间均无强连锁。结论 TLR2基因的5个SNP多态性与中国汉族儿童TB易感性不存在关联。

Objective To investigate the association between polymorphisms of Toll like receptor 2 ( TLR2 ) gene and tuberculosis( TB)in Chinese Han children. Methods A case-control study was performed in TB patients obtained from pediatric patients with TB admitted to Beijing Children's Hospital between February 2005 and October 2010,and other lung infection was excluded. TB patients were diagnosed as pulmonary TB( PTB),extrapulmonary TB( EPTB),severe tuberculosis( SevTB)and non-severe tuberculosis( NonSevTB ). Healthy controls were performed in health examination Chinese Han children,and TB infection was excluded. MassARRAY was used to find the difference of 5 SNPs of TLR2 gene,including rs3804099( allele C/T), rs1898830( allele A/G),rs7656411( allele G/T),rs11935252( allele A/G),rs7696323( allele C/T)and genotyping between TB group and the healthy control group. Then the difference of genotypes between TB and the control groups detected with dominant heredity model and recessive heredity model was analyzed. Results ①TB group included 435 children,the mean age was 5. 6 years(SD 4. 7),male(n=219,63. 5%);PTB(n=151,43. 81%),EPTB(n=194);sevTB(n=155,44. 9%),NonsevTB(n=190). The control group enrolled 385 children with mean age 6. 1(SD 3. 8)years,males(n=226,58. 7%). Genotype frequen-cies of 5 SNPs in cases,controls and all subjects met Hardy-Weinberg equilibrium. No statistically significant differences in allelic and genotypic distributions of 5 SNPs were observed between TB and control groups(P=0. 154_0. 992). After adjustment by age and gender,the genotype of rs3804099( TC,CC)and the frequency of allele C were found no statistical significance compared with the control group(0. 929_1. 071);rs1898830( GA,GG)and the frequency of allele G were also found no significant difference compared with the control groups(OR =1. 110 _1. 411);rs7656411(GT,TT)and the frequency of allele T were found no statistical significance between TB and control group(OR=0. 812_1. 110);rs11935252(GA,GG)and the frequency of allele A were found no significant difference compared with the control group(OR=0. 497 _1. 189)and rs7696323(TT,CT)and the frequency of allele C were found no statistical significance compared with the control group(OR=0. 888_1. 034)(P>0. 05)too.② Neither in the dominant heredity model nor recessive heredity model,the genotype distribution of the 5 SNPs in cases group significantly differed from that in the control group,either in PTB subgroup or in EPTB subgroup(OR=0. 737 _1. 326). And same results were found in sevTB and nonsevTB subgroups(OR=0. 675_1. 248),P>0. 05.③No LD blocks were identified in the 5 SNPs'of TLR2. Conclusion SNPs of TLR2 genes were not associated with TB suseptibility in Chinese Han children.