4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
Clin Infect Dis. 2010 Jul 15;51(2):242-7. doi: 10.1086/653607.
BACKGROUND. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection. METHODS. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections. RESULTS. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of <100 cells/mm(3), those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a >3-fold increase in the odds ratio (OR) of any serious infection (OR, 6.33 vs OR, 1.83, P = .043). CONCLUSIONS. This study suggests an association between the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms and the occurrence of serious infections in HIV-1 infected patients with a history of nadir CD4 cell count of <100 cells/mm(3).
Toll 样受体 4（TLR4）是对各种微生物的固有免疫反应的一个重要组成部分。我们研究了 TLR4 多态性与获得人类免疫缺陷病毒（HIV-1）感染患者严重感染风险之间的关系。
在 199 名 HIV-1 感染患者的队列中确定 TLR4 Asp299Gly 和 Thr399Ile 单核苷酸多态性（SNPs）的存在，并评估它们与各种感染的发生之间的关系。
172 名患者为野生型纯合子；22 名患者（11%）为两种 SNP 的杂合子；4 名患者为 1 种多态性的杂合子；1 名患者为 Asp299Gly SNP 的杂合子和 Thr399Ile SNP 的纯合子。在 CD4 细胞计数<100 个/mm3 的患者中，与携带野生型基因型的患者相比，携带两种 SNP 的患者任何严重感染的优势比（OR）增加了 3 倍以上（OR，6.33 vs OR，1.83，P =.043）。
本研究表明，TLR4 Asp299Gly 和 Thr399Ile 多态性的存在与 CD4 细胞计数<100 个/mm3 的 HIV-1 感染患者发生严重感染有关。
