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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 of TLR2 gene SNPs with susceptibility to tuberculosis (TB) in Chinese Han children. Methods TB cases diagnosed and diagnosed in Beijing Children’s Hospital from February 2005 to October 2010 and excluded from other lung infections were divided into TB group and divided into lung TB subgroup and pulmonary extranodal subgroup according to the site and severity of infection TB subgroup and severe TB subgroup, non-severe subgroup TB; healthy children with and without TB as control group. Five SNP sites for the TLR2 gene were identified using the high-throughput Mass ARRAY technique: rs3804099 (allele C / T), rs1898830 (allele A / G), rs7656411 (allele G / T), rs11935252 Genotypes A / G and rs7696323 (allele C / T) were genotyped. The genotypes and allele frequencies of five SNPs were compared between TB group and control group, The recessive genetic model was used to analyze the genotype difference between each TB subgroup and the control group. Results A total of 345 TB patients (mean age 5.6 ± 4.7 years, 219 men) were included in the TB group. 151 patients (43.8%) had lung TB subgroup, 194 patients had sub-extrahepatic TB subgroup (155 patients), and 154 patients (44.9% 190 cases of severe TB subgroup. The control group of 385 cases, age (6.1 ± 3.8) years, 226 males. Hardy-Weinberg test suggested that the five SNPs of TLR2 gene in the TB group and the control group genotype distribution were in line with genetic balance (P = 0.154 ~ 0.992). After adjusting for age and sex, the frequency of TC, CC and C alleles in rs3804099 locus was significantly higher than that in the control group (OR = 0.929-1.071); the frequency of GA, GG and G allele in rs1898830 locus TB group and OR = 1.100-1.411; The frequency of GT, TT and T allele in rs7656411 group was significantly higher than that in control group (OR = 0.812-1.110); The frequency of GA, GG and A allele in rs11935252 OR = 0.497 ~ 1.189; The frequencies of CT, CC and C alleles in rs7656323 group were significantly different from those in control group (OR = 0.888 ~ 1.034, TB = 0.888 ~ 1.034, P <0.05 ). Five SNPs were analyzed according to dominant and recessive inheritance patterns. There was no significant difference between TB genotype and control group (P> 0.05). The two SNPs of 2TLR2 gene in the dominant or recessive inheritance model, genotype frequencies in lung TB subgroup, extra-pulmonary TB subgroup and control group, OR = 0.737 ~ 1.326; severe TB subgroup, non-severe Compared with control group, OR = 0.675 ~ 1.248 in TB subgroup and control group respectively. There was no significant difference (all P> 0.05). There were no strong linkage among the 5 SNP sites of 3TLR2 gene in all chromosomes. Conclusion There are no correlations between the five polymorphisms of TLR2 gene and TB susceptibility in Han Chinese children.