Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population

J Clin Endocrinol Metab. 2007 Jun;92(6):2358-62. doi: 10.1210/jc.2007-0031. Epub 2007 Mar 20.

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, chi(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / ethnology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / ethnology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Variation*
  • Genotype
  • Humans
  • Japan / epidemiology
  • Leukocytes, Mononuclear / metabolism
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Small Ubiquitin-Related Modifier Proteins / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • SUMO4 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Tumor Necrosis Factor-alpha