肿瘤坏死因子α诱导蛋白 3 基因单核苷酸多态性与中国北方汉族人群类风湿关节炎易感性相关。
Single nucleotide polymorphisms in TNFAIP3 were associated with the risks of rheumatoid arthritis in northern Chinese Han population.
机构信息
Department of Rheumatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
出版信息
BMC Med Genet. 2014 May 15;15:56. doi: 10.1186/1471-2350-15-56.
BACKGROUND
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. It is well known that genetic and environmental risk factors and their interaction contribute to RA pathogenesis. This study aimed to investigate the association between the critical polymorphisms in the tumor necrosis factor α (TNFα)-induced protein 3(TNFAIP3) gene and the risk of RA in a large northern Chinese Han population.
METHODS
A case-control study of 1280 RA patients and 1280 matched healthy controls was conducted.
RESULTS
This study showed that carriers of the rs2230926 TG genotype or rs10499194 CT genotype had an increased risk for RA compared with those carrying the wild genotype (rs2230926: OR = 1.48, 95% CI = 1.17-1.86, p = 0.001; rs10499194: OR = 2.00, 95% CI = 1.46-2.74, p < 0.001). The combined rs2230926TG/GG or rs10499194 CT/TT were associated with an increased risk of RA (ORs were 1.50 and 2.01, 95% CIs were 1.19-1.88 and 1.47-2.74, respectively, both p < 0.001). There was not significant association between rs13207033 polymorphism and RA risk. Subset analysis stratified to gender showed that the increased risks were significant among the genotypes TG, TG/GG of rs2230926 and CT, CT/TT of rs10499194 and the corresponding ORs were 1.42 (95% CI = 1.10-1.83, p = 0.006), 1.44(95% CI = 1.12-1.85, p = 0.004), 1.52(95% CI = 1.05-2.20, p = 0.026) and 1.52(95% CI = 1.06-2.19, p = 0.023) in the female population. Stratified analyses by age found that rs2230926(TG, TG/GG) and rs10499194(CT, CT/TT) polymorphisms were associated with RA risks in population ≤53 years old and among >53 years old only rs10499194(CT, TT, CT/TT) polymorphism had significant results. The interaction analysis suggested that individuals with both risk genotypes of the two SNPs have a higher elevated risk of RA than those with only one of them (ORs were 3.44 compared to 1.74 and 1.35). The haplotype results showed that individuals with the rs2230926G-rs13207033G-rs10499194C haplotype were associated with increased risks of RA (OR = 1.37, 95% CI = 1.08-1.74, p = 0.010).
CONCLUSIONS
Rs10499194 and rs2230926 polymorphisms in the TNFAIP3 gene region may be susceptibility factors for rheumatoid arthritis in the northern Chinese Han population.
背景
类风湿关节炎（RA）是一种以滑膜关节慢性破坏性炎症为特征的系统性自身免疫性疾病。众所周知，遗传和环境风险因素及其相互作用有助于 RA 的发病机制。本研究旨在探讨中国北方汉族人群肿瘤坏死因子α（TNFα）诱导蛋白 3（TNFAIP3）基因中关键多态性与 RA 发病风险的关系。
方法
采用病例对照研究，共纳入 1280 例 RA 患者和 1280 例匹配的健康对照。
结果
本研究显示，与携带野生基因型（rs2230926：OR=1.48，95%CI=1.17-1.86，p=0.001；rs10499194：OR=2.00，95%CI=1.46-2.74，p<0.001）相比，携带 rs2230926TG 基因型或 rs10499194CT 基因型的个体患 RA 的风险增加。rs2230926TG/GG 或 rs10499194CT/TT 基因型的联合与 RA 风险增加相关（OR 分别为 1.50 和 2.01，95%CI 分别为 1.19-1.88 和 1.47-2.74，均 p<0.001）。rs13207033 多态性与 RA 风险无显著相关性。按性别分层的亚组分析显示，rs2230926 的 TG、TG/GG 基因型和 rs10499194 的 CT、CT/TT 基因型与 RA 风险增加显著相关，相应的 OR 分别为 1.42（95%CI=1.10-1.83，p=0.006）、1.44（95%CI=1.12-1.85，p=0.004）、1.52（95%CI=1.05-2.20，p=0.026）和 1.52（95%CI=1.06-2.19，p=0.023），女性人群中 CT、CT/TT 基因型与 RA 风险增加显著相关。按年龄分层的分析发现，rs2230926（TG、TG/GG）和 rs10499194（CT、CT/TT）多态性与≤53 岁人群的 RA 风险相关，而在>53 岁人群中，仅 rs10499194（CT、TT、CT/TT）多态性有显著结果。交互分析表明，与仅携带其中一个风险基因型的个体相比，同时携带这两个 SNP 的两个风险基因型的个体患 RA 的风险更高（OR 分别为 3.44 比 1.74 和 1.35）。单体型分析结果表明，rs2230926G-rs13207033G-rs10499194C 单体型与 RA 风险增加相关（OR=1.37，95%CI=1.08-1.74，p=0.010）。
结论
TNFAIP3 基因区域的 rs10499194 和 rs2230926 多态性可能是中国北方汉族人群类风湿关节炎的易感因素。
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