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


METHODS
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.
Noso
Shinsuke
S
Department of Endocrinology, Metabolism, and Diabetes, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, Japan.
Fujisawa
Tomomi
T
Kawabata
Yumiko
Y
Asano
Katsuaki
K
Hiromine
Yoshihisa
Y
Fukai
Aya
A
Ogihara
Toshio
T
Ikegami
Hiroshi
H
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014409:Tumor Necrosis Factor-alpha