title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Taro
authors.initials: T
authors.lastname: Maruyama
authors.forename: Koji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iizuka
authors.forename: Susumu
authors.initials: S
authors.lastname: Kurihara
authors.forename: Masataka
authors.initials: M
authors.lastname: Osaki
authors.forename: Miho
authors.initials: M
authors.lastname: Uga
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
mesh_terms: 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
chemical_list: D007328:Insulin