广东汉族正常人群TLR4基因单核苷酸多态性研究(英)

目的：人类Toll样受体4（TLR4）是先天免疫系统中一个重要的病原微生物识别受体。本研究将建立中国汉族正常人群TLR4基因座位的单核苷酸多态性图谱。方法：收集191例健康、无亲缘关系的中国广东汉族人外周血液，通过对TLR4基因的启动子区、3个外显子区以及它们周围的内含子区进行PCR扩增和测序，得到汉族正常人群TLR4基因座位单核苷酸多态性图谱及其频率分布特点。结果：共发现8个单核苷酸多态性位点，其中5个是首次发现的新位点。分布频率最高（0.283）的单核苷酸多态性位点是-1607 C/T。常见于高加索人中的2个非同义突变Asp299Gly和Thr399Ile在汉族人中没有被发现。中性检验显示汉族人群TLR4基因符合中性进化模型。结论：本研究建立了汉族正常人群TLR4基因座位的单核苷酸多态性图谱，发现了一些种族特异性的单核苷酸多态性位点，这些工作将为今后开展汉族人基因多态性与疾病相关性研究以及人群进化研究提供一定的帮助。

Single nucleotide polymorphisms of TLR4 locus in Chinese Cantonese population

AIM: Toll-like receptor 4 (TLR4) was an important pathogen recognition receptor in the innate immune system. The aim of this study was to investigate the distribution of TLR4 polymorphisms in the general population of China. METHODS: Peripheral blood samples were collected from 191 unrelated healthy Chinese Cantonese individuals. The functional regions of TLR4 locus, including promoter region and all three exons with their surrounding intronic regions were amplified using polymerase chain reaction. After purified, the amplified products were directly sequenced on both strands. RESULTS: A total of eight single nucleotides polymorphisms (SNPs) were detected, five of which were novel. The most common SNP were -1607 C/T with the minor allele frequency of 0.283. Two nonsynonymous substitutions Asp299Gly and Thr399Ile, which were common in Caucasus, were not detected in Cantonese. Neutrality test revealed that TLR4 in Chinese Cantonese was not significantly deviated from the neutral model. CONCLUSION: This is the new finding on the distribution of TLR4 SNPs in the general population of China. It provides several ethnic specific SNPs for further disease association studies of TLR4 polymorphisms in Chinese populations.