Tsurumaru Masako, Kawasaki Eiji, Ida Hiroaki, Migita Kiyoshi, Moriuchi Akie, Fukushima Keiko, Fukushima Tetsuya, Abiru Norio, Yamasaki Hironori, Noso Shinsuke, Ikegami Hiroshi, Awata Takuya, Sasaki Hitoshi, Eguchi Katsumi
Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
J Clin Endocrinol Metab. 2006 Aug;91(8):3138-43. doi: 10.1210/jc.2006-0206. Epub 2006 May 30.
Recently, an association of a single nucleotide polymorphism, 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for nuclear factor kappaB, has been reported in type 1 diabetes.
To establish whether SUMO4 locus contributes to the genetic susceptibility to other autoimmune disorders, a case-control analysis was carried out using genomic DNA from type 1 diabetes, autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), and primary Sjögren's syndrome.
A total of 1480 samples, including 929 cases (411 patients with type 1 diabetes, 292 AITD, 172 RA, and 54 primary Sjögren's syndrome) and 551 healthy control subjects of Japanese origin participated in the study.
The 163A>G (rs237025, M55V) polymorphism of SUMO4 was genotyped.
SUMO4 M55V variant was associated not only with type 1 diabetes [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.09-1.84; P = 0.0072], but also with increased risk of other autoimmune diseases, AITD (OR, 1.52; 95% CI, 1.14-2.03; P = 0.0041) and RA without amyloidosis (OR, 1.53; 95% CI, 1.65-2.24; P = 0.027), but not primary Sjögren's syndrome. Furthermore, the association of SUMO4 M55V variant was stronger in type 1 diabetic patients complicated with AITD (OR, 1.62; 95% CI, 1.06-2.47; P = 0.023) and in patients who have neither type 1 diabetes-susceptible class II HLA, DRB10405 nor DRB10901 (OR, 2.28; 95% CI, 1.34-3.87; P = 0.0018).
These results indicate that the SUMO4 is a more common autoimmune disease gene and a supplementary risk factor to type 1 diabetes in conjunction with class II HLA.
最近，已报道1型糖尿病中一种单核苷酸多态性，即SUMO4基因中编码M55V的163A>G，该基因已被证明是核因子κB的负反馈调节因子。
为确定SUMO4基因座是否与其他自身免疫性疾病的遗传易感性有关，使用1型糖尿病、自身免疫性甲状腺疾病（AITD）、类风湿关节炎（RA）和原发性干燥综合征患者的基因组DNA进行了病例对照分析。
共有1480份样本参与了该研究，其中包括929例病例（411例1型糖尿病患者、292例AITD患者、172例RA患者和54例原发性干燥综合征患者）以及551名日本裔健康对照者。
对SUMO4基因的163A>G（rs237025，M55V）多态性进行基因分型。
SUMO4 M55V变异不仅与1型糖尿病相关[比值比（OR）为1.42；95%置信区间（CI）为1.09 - 1.84；P = 0.0072]，还与其他自身免疫性疾病风险增加有关，如AITD（OR为1.52；95% CI为1.14 - 2.03；P = 0.0041）和无淀粉样变性的RA（OR为1.53；95% CI为1.65 - 2.24；P = 0.027），但与原发性干燥综合征无关。此外，SUMO4 M55V变异在合并AITD的1型糖尿病患者（OR为1.62；95% CI为1.06 - 2.47；P = 0.023）以及既没有1型糖尿病易感的II类HLA、DRB10405也没有DRB10901的患者中关联更强（OR为2.28；95% CI为1.34 - 3.87；P = 0.0018）。
这些结果表明，SUMO4是一种更常见的自身免疫性疾病基因，并且是与II类HLA共同作用的1型糖尿病的补充风险因素。
