Context: Despite distinct difference in the pathogenesis, epidemiological data have indicated familial clustering of type 1 and type 2 diabetes, suggesting a common genetic basis between these two types of diabetes. Few shared susceptibility genes, however, have been reported to date.

Objective: Small ubiquitin like modifier 4 (SUMO4) has been identified as a candidate gene for the IDDM5 locus, and suggested to have possible involvement in immune responses, such as autoimmunity and inflammation. Recent reports demonstrated that a polymorphism with an amino acid substitution (Met55Val) in SUMO4 was associated with type 1 diabetes in Asian populations, although no association was reproduced in subjects of Caucasian descent. The present study aimed to clarify the contribution of SUMO4 to type 2 diabetes susceptibility in the Japanese population.

Subjects: The 753 subjects included 355 cases and 398 control subjects.

Methods: The SUMO4 Met55Val (rs237025) and 001Msp (rs577001) polymorphisms were genotyped.

Results: Strong linkage disequilibrium (D': 1.0 in each pair of SNPs) across the MAP3K7IP2/SUMO4 region was shown in the Japanese population. The frequency of genotypes with the G allele of the SUMO4 Met55Val polymorphism was significantly higher in patients with type 2 diabetes (odds ratio [95%CI]: 1.46 [1.08-1.93], p=0.01, ² test). The association was concentrated in patients without insulin therapy (odds ratio: 1.56 [1.13-2.15], p=0.0072), but not in those with insulin (odds: 1.24 [0.81-1.89], NS).

Conclusions: These data, together with previous reports, suggest the contribution of the SUMO4 Met55Val polymorphism to both type 1 and type 2 diabetes susceptibility in the Japanese population.