Molecular and Genetic Epidemiology Laboratory, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Arthritis Res Ther. 2010;12(5):R174. doi: 10.1186/ar3134. Epub 2010 Sep 17.
TNFAIP3 interacting protein 1, TNIP1 (ABIN-1) is involved in inhibition of nuclear factor-κB (NF-κB) activation by interacting with TNF alpha-induced protein 3, A20 (TNFAIP3), an established susceptibility gene to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recent genome-wide association studies revealed association of TNIP1 with SLE in the Caucasian and Chinese populations. In this study, we investigated whether the association of TNIP1 with SLE was replicated in a Japanese population. In addition, association of TNIP1 with RA was also examined.
A case-control association study was conducted on the TNIP1 single nucleotide polymorphism (SNP) rs7708392 in 364 Japanese SLE patients, 553 RA patients and 513 healthy controls.
Association of TNIP1 rs7708392C was replicated in Japanese SLE (allele frequency in SLE: 76.5%, control: 69.9%, P = 0.0022, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.13-1.74). Notably, the risk allele frequency in the healthy controls was considerably greater in Japanese (69.9%) than in Caucasians (24.3%). A tendency of stronger association was observed in the SLE patients with renal disorder (P = 0.00065, OR 1.60 [95%CI 1.22-2.10]) than in all SLE patients (P = 0.0022, OR 1.40 [95%CI 1.13-1.74]). Significant association with RA was not observed, regardless of the carriage of human leukocyte antigen DR β1 (HLA-DRB1) shared epitope. Significant gene-gene interaction between TNIP1 and TNFAIP3 was detected neither in SLE nor RA.
Association of TNIP1 with SLE was confirmed in a Japanese population. TNIP1 is a shared SLE susceptibility gene in the Caucasian and Asian populations, but the genetic contribution appeared to be greater in the Japanese and Chinese populations because of the higher risk allele frequency. Taken together with the association of TNFAIP3, these observations underscore the crucial role of NF-κB regulation in the pathogenesis of SLE.
肿瘤坏死因子-α诱导蛋白 3 相互作用蛋白 1（TNFAIP3IP1，也称为 ABIN-1）通过与肿瘤坏死因子-α诱导蛋白 3（TNFAIP3）相互作用抑制核因子-κB（NF-κB）激活，是系统性红斑狼疮（SLE）和类风湿关节炎（RA）的易感基因。最近的全基因组关联研究显示，TNIP1 与高加索人群和中国人群的 SLE 相关。在这项研究中，我们调查了在日本人群中，TNIP1 与 SLE 的关联是否得到了复制。此外，还研究了 TNIP1 与 RA 的关联。
对 364 例日本 SLE 患者、553 例 RA 患者和 513 例健康对照进行了 TNIP1 单核苷酸多态性（SNP）rs7708392 的病例对照关联研究。
在日本 SLE 中，TNIP1 rs7708392C 的关联得到了复制（SLE 组的等位基因频率为 76.5%，对照组为 69.9%，P=0.0022，比值比 [OR] 为 1.40，95%置信区间 [CI] 为 1.13-1.74）。值得注意的是，日本人群中健康对照的风险等位基因频率明显高于高加索人群（69.9%比 24.3%）。在有肾脏疾病的 SLE 患者中（P=0.00065，OR 1.60 [95%CI 1.22-2.10]），这种关联趋势比所有 SLE 患者（P=0.0022，OR 1.40 [95%CI 1.13-1.74]）更强。无论是否携带人类白细胞抗原 DRβ1（HLA-DRB1）共享表位，与 RA 均无显著关联。在 SLE 和 RA 中均未检测到 TNIP1 与 TNFAIP3 之间的显著基因-基因相互作用。
在日本人群中证实了 TNIP1 与 SLE 的关联。TNIP1 是高加索人群和亚洲人群共有的 SLE 易感基因，但由于风险等位基因频率较高，在日本和中国人群中的遗传贡献似乎更大。结合 TNFAIP3 的关联，这些观察结果强调了 NF-κB 调节在 SLE 发病机制中的关键作用。
