Context: Recently, an association of a single nucleotide polymorphism (SNP), 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for NF-B, has been reported in type 1 diabetes.

Objective: To establish whether SUMO4 locus contributes toward 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.

Subjects: A total of 1,480 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.

Methods: The 163A>G (rs237025, M55V) polymorphism of SUMO4 was genotyped.

Results: SUMO4 M55V variant was associated not only with type 1 diabetes (odds ratio (OR): 1.42 [95%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, DRB1*0405 nor DRB1*0901 (OR 2.28 [95%CI 1.34-3.87], P = 0.0018).

Conclusions: 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.