CAJ | 학술논문

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 MassARRAY 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。目的：探討TLR2基因5箇SNP位點多態性與中國漢族兒童結覈病（ TB）易感性的關聯。方法以2005年2月至2010年10月在北京兒童醫院臨床診斷和確診的TB且排除其他肺部感染的病例作為TB組，併根據感染部位和嚴重程度分彆分為肺TB亞組、肺外TB亞組和重癥TB亞組、非重癥TB亞組；以健康查體且除外TB的兒童作為對照組。應用高通量 MassARRAY 技術對于 TLR2基因的5箇 SNP 位點：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，比較5箇SNP位點各基因型和等位基因頻率在TB組和對照組的差異，同時採用顯性遺傳和隱性遺傳模式分析各TB亞組與對照組基因型的差異。結果 TB組345例，平均年齡（5.6±4.7）歲，男219例；肺TB亞組151例（43.8%），肺外TB亞組194例；重癥TB亞組155例（44.9%），非重癥TB亞組190例。對照組385例，年齡（6.1±3.8）歲，男226例。Hardy-Weinberg檢驗提示TLR2基因的5箇SNP位點在TB組和對照組的基因型分佈均符閤遺傳平衡（ P=0.154~0.992）。調整瞭年齡和性彆因素後， rs3804099位點TC、CC型和C等位基因頻率TB組和對照組比較，OR=0.929~1.071；rs1898830位點GA、GG型和G等位基因頻率TB組和對照組比較，OR=1.100~1.411；rs7656411位點GT、TT型和T等位基因頻率TB組和對照組比較，OR=0.812~1.110；rs11935252位點GA、GG型和A等位基因頻率TB組和對照組比較，OR=0.497~1.189；rs7656323位點CT、CC型和C等位基因頻率TB組和對照組比較，OR=0.888~1.034；，差異均無統計學意義（ P均>0.05）。5箇SNP按照顯性和隱性遺傳模式分析，各基因型TB組和對照組間差異均無統計學意義（ P均>0.05）。②TLR2基因的5箇SNP位點在顯性或隱性遺傳模式下，基因型頻率在肺TB亞組、肺外TB亞組和對照組比較，OR=0.737~1.326；重癥TB亞組、非重癥TB亞組和對照組比較，OR=0.675~1.248；差異均無統計學意義（ P均>0.05）。③TLR2基因5箇SNP位點在各染色體之間均無彊連鎖。結論 TLR2基因的5箇SNP多態性與中國漢族兒童TB易感性不存在關聯。
목적：탐토TLR2기인5개SNP위점다태성여중국한족인동결핵병（ TB）역감성적관련。방법이2005년2월지2010년10월재북경인동의원림상진단화학진적TB차배제기타폐부감염적병례작위TB조，병근거감염부위화엄중정도분별분위폐TB아조、폐외TB아조화중증TB아조、비중증TB아조；이건강사체차제외TB적인동작위대조조。응용고통량 MassARRAY 기술대우 TLR2기인적5개 SNP 위점：rs3804099（등위기인 C/T ）、rs1898830（등위기인 A/G ）、rs7656411（등위기인G/T）、rs11935252（등위기인A/G）、rs7696323（등위기인C/T）행기인분형，비교5개SNP위점각기인형화등위기인빈솔재TB조화대조조적차이，동시채용현성유전화은성유전모식분석각TB아조여대조조기인형적차이。결과 TB조345례，평균년령（5.6±4.7）세，남219례；폐TB아조151례（43.8%），폐외TB아조194례；중증TB아조155례（44.9%），비중증TB아조190례。대조조385례，년령（6.1±3.8）세，남226례。Hardy-Weinberg검험제시TLR2기인적5개SNP위점재TB조화대조조적기인형분포균부합유전평형（ P=0.154~0.992）。조정료년령화성별인소후， rs3804099위점TC、CC형화C등위기인빈솔TB조화대조조비교，OR=0.929~1.071；rs1898830위점GA、GG형화G등위기인빈솔TB조화대조조비교，OR=1.100~1.411；rs7656411위점GT、TT형화T등위기인빈솔TB조화대조조비교，OR=0.812~1.110；rs11935252위점GA、GG형화A등위기인빈솔TB조화대조조비교，OR=0.497~1.189；rs7656323위점CT、CC형화C등위기인빈솔TB조화대조조비교，OR=0.888~1.034；，차이균무통계학의의（ P균>0.05）。5개SNP안조현성화은성유전모식분석，각기인형TB조화대조조간차이균무통계학의의（ P균>0.05）。②TLR2기인적5개SNP위점재현성혹은성유전모식하，기인형빈솔재폐TB아조、폐외TB아조화대조조비교，OR=0.737~1.326；중증TB아조、비중증TB아조화대조조비교，OR=0.675~1.248；차이균무통계학의의（ P균>0.05）。③TLR2기인5개SNP위점재각염색체지간균무강련쇄。결론 TLR2기인적5개SNP다태성여중국한족인동TB역감성불존재관련。
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.