目的:人类Toll样受体1(TLR1)在先天性免疫中起着重要作用.本文将着重研究广东地区汉族正常人群中TLR1基因功能区的单核苷酸多态性(SNPs)图谱和频率分布.方法:随机收集50例健康、无亲缘关系的中国广东地区汉族人外周血液,对TLR1基因的启动子区、5和3非翻译区、4个外显子区的序列进行PCR扩增和直接测序,找出多态性位点及其频率分布规律.在此基础上对多态性位点进行Hardy-Weinberg平衡分析、中性进化分析和连锁不平衡分析.结果:共发现17个SNPs以及2个插入/缺失多态位点,其中2个是首次发现的新多态性位点.位于编码区的新SNP位点+1 378 A/G为非同义突变位点,能导致460位丝氨酸(Ser)残基替换为甘氨酸(Gly)残基,并且这个氨基酸残基的替换处于TLR1胞外区的LRR结构域中,从而有可能影响蛋白的识别功能.另外,频率最高的SNPs是+743 A/G和+1 518 A/G,其次要等位基因频率均达到48%.所有多态性位点均符合Hardy-Weinberg平衡.中性检验显示广东汉族人群TLR1基因不符合中性进化假说,很可能是其调控区受到平衡选择作用的原因.连锁不平衡分析显示多态性位点-6 912 C/TA、-6 876 C/T、-6 399 C/T和-6 375 C/T之间,-6 847 A/G和-6 737 A/T之间,以及-5 984 -/CT、-5 531 A/G和-5 490 C/G之间完全连锁.结论:本研究首次报道了汉族正常人群TLR1基因的功能性多态性图谱,发现了一些种族特异性的多态性位点及频率分布规律,为今后开展汉族人基因多态性与疾病相关性研究打下一定的基础.%AIM: To investigate the distribution of Toll - like receptor 1 ( TLR1) polymorphisms in Cantonese Han population. METHODS; Peripheral blood samples were collected from 50 unrelated healthy Chinese Cantonese Han individuals. The functional regions of TLR1 locus, including promoter region, 5' UTR, all 4 exons and 3' UTR, were amplified and sequenced. RESULTS: A total of 17 single nucleotide polymorphisms (SNPs) and 2 insertions and deletions were detected, two of which were novel. SNP -I-1 378 A/C located in the coding region was a nonsynonymous substitution, which could cause ami no acid substitution from Ser to Gly at coden 460. The most common SNPs were +743 A/G and + 1 518 A/G with the minor allele frequency of 48%. All polymorphic sites were consistent with Hardy - Weinberg equilibrium. Neutrality test showed that TLRJ in Cantonese Han population was significantly deviated from the neutral model, suggesting that the polymorphisms of promoter region might be caused by balancing selection. Linkage disequilibrium( LD) analysis showed complete LD between -6 912 C/TA, -6 876 C/T, -6 399 C/T and -6 375 C/T, between -6 847 A/ G and -6 737 A/T, and between -5 984 -/CT, -5 531 A/G and -5 490 C/G. CONCLUSION: This is a first report about the distribution of TLR1 functional polymorphisms in the general population of China. It provides some ethnicspecific polymorphisms and frequency - distribution characteristics, which might help in the further disease association studies in Chinese.
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