We analyzed clinical and genetic factors contributing to infections in 457 subjects with early rheumatoid arthritis (RA) enrolled in a prospective, 1-year clinical trial of methotrexate and the TNF inhibitor etanercept. Subjects were genotyped for the following single nucleotide polymorphisms (SNPs): (TNF -308, -238, and + 488); lymphotoxin-alpha (LTA) (LTA + 249, + 365, and + 720); and Fc gamma receptors FCGR2A 131 H/R; FCGR3A 176 F/V; and FCGR3B NA 1/2 and genotypes were correlated with infections. At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P = 0.038). Urinary tract infection (UTI) was associated with the TNF -238 A (odds ratio(OR) 2.56, 95% confidence interval (CI) 1.05-6.25) and LTA +365 C (OR 1.73, 95% CI 1.07-2.79) alleles, and marginally with the FCGR3A F allele (OR 1.72, 95% CI 0.99-3.00). There was a striking linear correlation between UTI and the number of risk alleles defined by these three SNPs (P < 0.001), suggesting an additive effect on susceptibility. These findings have important implications for the role of genetics in susceptibility to bacterial and viral infections.

中文翻译：

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遗传风险因子感染患者早期类风湿性关节炎。

我们分析了有助于在457名受试者早期类风湿关节炎（RA）感染的临床和遗传因素就读于氨甲喋呤的前瞻性，1年的临床试验和TNF抑制剂依那西普。受试者进行基因分型为以下的单核苷酸多态性（SNP）：（TNF -308，-238，和+ 488）; 淋巴毒素-α（LTA）（LTA + 249，+ 365，和+ 720）; 和Fcγ受体FCGR2A 131 H / R; FCGR3A 176 F / V; 和FCGR3B NA 1/2和基因型与感染相关。至少一个URI指出的受试者（191分之99）与嗜中性粒细胞特异性基因FCGR3B的NA2 / NA2基因型52％，比起那些与NA1 / NA2基因型和39％的42％（181分之77）那些与NA1 / NA1基因型（P = 0.038）的（59分之23）。尿路感染（UTI）与TNF -238 A（比值比（OR）2.56相关联，95％置信区间（CI）1.05-6.25）和LTA 365 C（OR 1.73，95％CI 1.07-2.79）等位基因，和边缘与FCGR3A˚F等位基因（OR 1.72，95％CI 0.99-3.00）。有UTI和由这三个单核苷酸多态性定义风险等位基因的（P 0.001 <）的数量之间的显着的线性相关性，表明对敏感性的添加剂的效果。这些发现对遗传学的敏感性的作用，细菌和病毒感染具有重要意义。