Insulin gene/IDDM2 locus in Japanese type 1 diabetes: contribution of class I alleles and influence of class I subdivision in susceptibility to type 1 diabetes.
BACKGROUND
It is suggested that insulin autoimmunity plays an important role in the development of type 1 diabetes in humans. However, the association between insulin gene (INS) region (IDDM2) and type 1 diabetes has been uncertain in Asians.


OBJECTIVE
A multicenter collaboration study was conducted to clarify the role of the IDDM2 region in Japan.


METHODS
In total, 661 patients with type 1 diabetes and 706 control subjects were enrolled. The INS variable number of tandem repeat (VNTR) class I/class III status was estimated by genotyping the -23 HphI single nucleotide polymorphism. From surrounding polymorphisms across the insulin gene, we also inferred haplotypes bearing INS VNTR lineages.


RESULTS
The frequency of the class I allele was 99.3% in patients and 96.7% in controls (P < 10(-5)), and the class I/III or III/III genotype was found in 1.4% of patients and in 6.4% of controls [odds ratio (OR) 0.20, P < 10(-5)]. The class I subdivision revealed IC to increase significantly in patients with type 1 diabetes (P = 0.002), whereas ID did not; the distribution of IC and ID was significantly different between patients and controls (P = 0.014).


CONCLUSIONS
The present study certainly shows that the IDDM2 region is also a susceptibility locus in the Japanese population. Furthermore, it was revealed that IC may be more susceptible to type 1 diabetes than ID, which could be evidence that the INS VNTR itself confers susceptibility to type 1 diabetes.
Awata
Takuya
T
Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan. awata@saitama-med.ac.jp.
Kawasaki
Eiji
E
Ikegami
Hiroshi
H
Kobayashi
Tetsuro
T
Maruyama
Taro
T
Nakanishi
Koji
K
Shimada
Akira
A
Iizuka
Hiroyuki
H
Kurihara
Susumu
S
Osaki
Masataka
M
Uga
Miho
M
Kawabata
Yumiko
Y
Tanaka
Shoichiro
S
Kanazawa
Yasuhiko
Y
Katayama
Shigehiro
S
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D007328:Insulin