Thurow Helena Strelow, Sarturi Cladinara Roberts, Fallavena Paulo Roberto Vargas, Paludo Francis Jackson de Oliveira, Picanço Juliane Bentes, Fraga Lucas Rosa, Graebin Pietra, de Souza Vinícius Carolino, Dias Fernando Suparregui, Nóbrega Otávio de Tolêdo, Alho Clarice Sampaio
Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
Genet Test Mol Biomarkers. 2010 Jun;14(3):405-19. doi: 10.1089/gtmb.2009.0169.
Toll-like receptor 2 (TLR2) is a recognition receptor for the widest repertoire of pathogen-associated molecular patterns. Two polymorphisms of TLR2 could be linked to reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and to increased risk of infection (supposed-2029C>T and 2258G>A). We investigated the supposed-2029C>T and 2258G>A TLR2 polymorphisms in 422 critically ill patients of European origin from southern Brazil (295 with sepsis and 127 without sepsis) and reviewed 33 studies on these polymorphisms, conducting a quality assessment with a score system. Among our patients we found only one heterozygote (1/422) for the supposed-2029C>T and none for the 2258G>A (0/422) single nucleotide polymorphism (SNP). We were unable to find a clinical application of supposed-2029T and 2258A allele analyses in our southern Brazilian population. Our review detected that current TLR2 SNP assays had very controversial and contradictory results derived from reports with a variety of investigation quality criteria. We suggest that, if analyzed alone, the supposed-2029C>T and 2258G>A TLR2 SNP are not good candidates for genetic markers in studies that search for direct or indirect clinical applications between genotype and phenotype. Future efforts to improve the knowledge and to provide other simultaneous genetic markers might reveal a more effective TLR2 effect on the susceptibility to infectious diseases.
Toll样受体2（TLR2）是识别种类最为广泛的病原体相关分子模式的受体。TLR2的两种多态性可能与活化B细胞核因子κB（NF-κB）激活减少及感染风险增加有关（推测的-2029C>T和2258G>A）。我们对来自巴西南部的422名欧洲裔危重症患者（295例脓毒症患者和127例非脓毒症患者）的推测的-2029C>T和2258G>A TLR2多态性进行了研究，并回顾了33项关于这些多态性的研究，采用评分系统进行质量评估。在我们的患者中，我们仅发现1例推测的-2029C>T杂合子（1/422），而2258G>A单核苷酸多态性（SNP）未发现杂合子（0/422）。我们未能在巴西南部人群中找到推测的-2029T和2258A等位基因分析的临床应用。我们的综述发现，目前的TLR2 SNP检测结果因各种研究质量标准的报告而极具争议且相互矛盾。我们建议，如果单独分析，推测 的-2029C>T和2258G>A TLR2 SNP并非寻找基因型与表型之间直接或间接临床应用的研究中理想的遗传标记候选物。未来为增进了解并提供其他同时存在的遗传标记所做的努力，可能会揭示TLR2对传染病易感性更有效的影响。
