title: CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).
  
  
  METHODS
  Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.
  
  
  RESULTS
  CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.
  
  
  CONCLUSIONS
  CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
authors.affiliation: Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Sun
authors.forename: Saikiran K
authors.initials: SK
authors.lastname: Sedimbi
authors.forename: Ayyappa K
authors.initials: AK
authors.lastname: Ashok
authors.forename: Carani B
authors.initials: CB
authors.lastname: Sanjeevi
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D013548:Sweden; D055815:Young Adult; D038203:alpha-Crystallin B Chain / Q000235:genetics*
chemical_list: D001323:Autoantibodies; C059215:CRYAB protein, human; D007328:Insulin; D038203:alpha-Crystallin B Chain