The rs878081 polymorphism of AIRE gene increases the risk of rheumatoid arthritis in a Chinese Han population: a case-control study

The autoimmune regulator (AIRE), a transcriptional regulator expressed in medullary thymic epithelial cells, plays an important role in thymocyte education and negative selection. Several citations studying the association between the rs878081 exon polymorphism of the AIRE gene and the risk of rheumatoid arthritis (RA) in different populations have yielded conflicting findings. Thus, this case-control study involving 300 RA cases and 300 controls was aimed to identify whether such association existed in a Chinese Han population from East China. The rs878081 polymorphism of the AIRE gene was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, and stratification analysis. Genetic model analysis showed significant correlations between the TT genotype and the risk of RA (OR: 1.89, 95%CI: 1.03-3.47 in TT vs CC; OR: 1.84, 95%CI: 1.02-3.31 in TT vs CC+TC). Stratification analyses of sex, age, smoking, and alcoholism suggested that the rs878081 polymorphism of the AIRE gene increased RA risk among non-smokers. In conclusion, rs878081 polymorphism of AIRE gene increases the risk of RA in a Chinese Han population.

自身免疫调节因子（autoimmune regulator, AIRE）是一种在胸腺髓质上皮细胞中表达的转录调控因子，在胸腺细胞教育与阴性选择过程中发挥重要作用。目前已有多项针对不同人群中AIRE基因rs878081外显子多态性与类风湿关节炎（rheumatoid arthritis, RA）发病风险关联的研究，所得结论却相互矛盾。为此，本研究开展一项纳入300例RA病例与300例对照的病例对照研究，旨在明确中国华东地区汉族人群中二者是否存在关联。研究对AIRE基因rs878081多态性进行基因分型，采用卡方检验、遗传模型分析及分层分析估算比值比（odds ratios, ORs）与95%置信区间（95% confidence intervals, CIs）。遗传模型分析结果显示，TT基因型与RA发病风险存在显著相关性（TT vs CC：OR=1.89，95%CI=1.03~3.47；TT vs CC+TC：OR=1.84，95%CI=1.02~3.31）。针对性别、年龄、吸烟及酗酒情况的分层分析表明，AIRE基因rs878081多态性可升高非吸烟者的RA发病风险。综上，AIRE基因rs878081多态性会增加中国华东地区汉族人群的RA发病风险。