Lazarus Ross, Klimecki Walter T, Raby Benjamin A, Vercelli Donata, Palmer Lyle J, Kwiatkowski David J, Silverman Edwin K, Martinez Fernando, Weiss Scott T
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Genomics. 2003 Jan;81(1):85-91. doi: 10.1016/s0888-7543(02)00022-8.
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%CI 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.
Toll样受体9（TLR9）是一种哺乳动物Toll样受体同系物，它似乎作为一种天然免疫模式识别蛋白，识别在细菌DNA中比在哺乳动物DNA中更为常见的基序。对来自三个自我认定的美国种族群体的71名受试者的该基因进行了测序，以识别单核苷酸多态性（SNP）。共发现20个SNP，其中只有20%存在于公共的dbSNP数据库中。在所有三个种族样本中，有四个SNP相对常见。利用这四个SNP，经统计学推断出七种不同的单倍型，其中四种占75%或更多的染色体。这四种单倍型可通过两个SNP（-1237和2848）的等位基因相互区分。通过对从四项正在进行的队列研究中收集的DNA进行基因分型，开展了五项探索性巢式病例对照疾病关联研究（针对欧裔美国人的哮喘、深静脉血栓形成、心肌梗死和慢性阻塞性肺疾病，以及针对非裔美国人的哮喘）。有证据表明，在欧裔美国人中（可获得67例病例和152例对照的基因型），-1237位点的C等位基因会增加患哮喘的风险（优势比1.85，95%置信区间1.05至3.25）。未检测到其他显著的疾病关联。需要在其他更大的样本中重复这一发现。这项研究表明，人类TLR9存在大量多样性，可能与欧洲人的哮喘有关，但与非裔美国人无关。未检测到与其他三种可能与天然免疫相关的疾病存在关联。
