Association of Small Ubiquitin-Like Modifier 4 (SUMO4) Variant, Located in IDDM5 Locus, with Type 2 Diabetes in the Japanese Population

Abstract

Abstract Context: Despite distinct differences 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 single-nucleotide polymorphisms) 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, 1.46; 95% confidence interval (CI), 1.08–1.93; P = 0.01, χ2 test]. The association was concentrated in patients without insulin therapy (odds ratio, 1.56; 95% CI, 1.13–2.15; P = 0.0072), but not in those with insulin (odds ratio, 1.24; 95% CI, 0.81–1.89; not significant). 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.