Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9):: frequencies, pairwise linkage disequilibrium, and haplotypes in three US ethnic groups and exploratory case-control disease association studies
Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9):: frequencies, pairwise linkage disequilibrium, and haplotypes in three US ethnic groups and exploratory case-control disease association studies
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DOI：
10.1016/s0888-7543(02)00022-8
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发表时间：
2003-01-01
期刊：
影响因子：
4.4
通讯作者：
Weiss, ST
中科院分区：
文献类型：
--
作者：
Lazarus, R;Klimecki, WT;Weiss, ST
TLR9是一种哺乳动物Toll样受体同源物，它似乎是一种天然免疫模式识别蛋白，可以识别细菌中比哺乳动物DNA中更常见的基序。对来自三个自我确认的美国种族的71名受试者的该基因进行了测序，以确定单核苷酸多态(SNPs)。总共发现了20个SNP，其中只有20%在公共数据库中。在所有三个民族的样本中，四个SNP相对常见。利用这4个SNP，统计推断出7种不同的单倍型，其中4种单倍型占染色体的75%以上。根据两个SNPs的等位基因(-1237和2848)可以将这四种单倍型区分开来。五项探索性嵌套病例对照疾病关联研究(欧洲美国人中的哮喘、DVT、MI和COPD，以及非裔美国人中的哮喘)通过从四项正在进行的队列研究中收集的DNA进行了基因分型。有证据表明，在欧洲裔美国人中，C等位基因位于-1237(优势比1.85，95%CI 1.05至3.25)的人患哮喘的风险增加(67例患者和152名对照)。没有检测到其他重要的疾病关联。这一发现需要在其他更大的样本中复制。这项研究表明，人类TLR9基因存在相当大的多样性，可能与欧洲人的哮喘有关，但与非裔美国人的哮喘无关。没有发现与其他三种可能与先天免疫有关的疾病有关。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
TLR9 is a mammalian Toll-like receptor homologue that appears to function as an innate immune pattern recognition protein for motifs that are far more common in bacterial than in mammalian DNA. The gene was sequenced in 71 subjects from three self-identified U.S. ethnic groups to identify single-nucleotide polymorphisms (SNPs). A total of 20 SNPs were found of which only 20% were in the public dbSNP database. Four SNPs were relatively common in all three ethnic samples. Using these four SNPs, seven distinct haplotypes were statistically inferred, of which four accounted for 75% or more chromosomes. These four haplotypes could be distinguished from each other by the alleles of two SNPs (- 1237 and 2848). Five exploratory nested case-control disease-association studies (asthma, DVT, MI, and COPD in European Americans and asthma in African Americans) were performed by genotyping DNA collected from four ongoing cohort studies. There was evidence suggesting increased risk for asthma with a C allele at - 1237 (odds ratio 1.85, 95%Cl 1.05 to 3.25) among European Americans (genotypes available from 67 cases and 152 controls). No other significant disease associations were detected. Replication of this finding in other, larger samples is needed. This study suggests that there is substantial diversity in human TLR9, possibly associated with asthma in Europeans but not African Americans. No association was detected with three other diseases potentially related to innate immunity. (C) 2003 Elsevier Science (USA). All rights reserved.