Genetic association between the interleukin-2 receptor-alpha gene and mode of onset of type 1 diabetes in the Japanese population.
OBJECTIVE
The IL-2 receptor-alpha (IL2RA), also known as CD25, is expressed on the regulatory T cells, which play an important role in the control of immune responses and the maintenance of immune homeostasis. Our objective was to determine whether variants in the IL2RA gene are associated with type 1 diabetes in the Japanese population.


METHODS
We genotyped the four single-nucleotide polymorphisms (rs706778, rs3118470, ss52580101, and rs11594656) of the IL2RA in 885 patients with type 1 diabetes and 606 control subjects of Japanese origin. The allele and genotype frequencies were examined in the patient groups stratified by their mode of onset in a case-control study.


RESULTS
We found evidence of association with acute-onset, but not slow-onset and fulminant, type 1 diabetes for two of the four single-nucleotide polymorphisms genotyped (rs706778 and rs3118470). The rs706778 A allele and the rs3118470 G allele were associated with an increased disease risk [odds ratio (OR) for rs706778 AA genotype 1.54, P = 4.2 x 10(-4) and OR for rs3118470 GG genotype 1.50, P = 0.0019, respectively]. Furthermore, the A-G haplotype was associated with increased type 1 diabetes risk in the acute-onset form (OR 1.30, P = 0.002).


CONCLUSIONS
The present data confirm the type 1 diabetes association with IL2RA and provide evidence that the different contributions of the IL2RA in the susceptibility to acute-onset and other forms of type 1 diabetes in the Japanese population.
Kawasaki
Eiji
E
Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. eijikawa@nagasaki-u.ac.jp
Awata
Takuya
T
Ikegami
Hiroshi
H
Kobayashi
Tetsuro
T
Maruyama
Taro
T
Nakanishi
Koji
K
Shimada
Akira
A
Uga
Miho
M
Kurihara
Susumu
S
Kawabata
Yumiko
Y
Tanaka
Shoichiro
S
Kanazawa
Yasuhiko
Y
Eguchi
Katsumi
K
D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide
D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit