title: Autoimmune diabetes mellitus with adult onset and type 1 diabetes mellitus in children have different genetic predispositions.
abstract: Type 1 diabetes with manifestation after 35 years of age is defined by CP <200 pmol/L and institution of insulin therapy within 6 months after diagnosis. Latent autoimmune diabetes mellitus in adults (LADA) manifesting after 35 years of age is defined by minimum 6 months after diagnosis without insulin therapy and C peptide (CP) >200 pmol/L and antiGAD > 50 ng/mL. We aimed to find a possible genetic discrimination among different types of autoimmune diabetes. To accomplish this goal, we analyzed DNA samples from 31 LADA patients, 75 patients with adult-onset type 1 diabetes mellitus, 188 type 1 diabetic children, and 153 healthy adult individuals. We studied five genetic loci on chromosomes 6, 11, 4, and 14: HLA DRB1 and DQB1 alleles, major histocompatibility complex (MHC) class I-related gene-A (MIC-A) microsatellite polymorphism, interleukin (IL)-18 single nucleotide polymorphism, the microsatellite polymorphism of nuclear factor kappa B gene (NF-kappaB1), and the single nucleotide polymorphism of a gene for its inhibitor (NF-kappaBIA). HLA-DR3 was detected as the predisposition allele for LADA (OR = 4.94, P < 0.0001). Further we found a statistically significant increase of NF-kappaBIA AA genotype (OR = 2.68, P < 0.01). On the other hand, DRB1*04, which is linked with DQB1*0302, was observed as a risk factor in patients with type 1 diabetes mellitus (T1DM) onset after 35 years of age (OR = 10.47, P < 0.0001 and OR = 9.49, P < 0.0001, respectively). There was also an association with MIC-A5.1 (OR = 2.14, P < 0.01). Statistically significant difference was found in the distribution of IL-18 promoter -607 (C/A) polymorphism between LADA and T1DM in adults (P < 0.01). We conclude that all subgroups of autoimmune diabetes have partly different immunogenetic predisposition.
authors.affiliation: Department of Cellular and Molecular Biology, Centrum for Diabetes, Metabolism and Nutrition Research of Third Faculty of Medicine, Charles University in Prague, Ruska 87, 100-00, Praha 10, Czech Republic. marie.cerna@lf3.cuni.cz
authors.forename: Marie
authors.initials: M
authors.lastname: Cerna
authors.forename: Katarina
authors.initials: K
authors.lastname: Kolostova
authors.forename: Peter
authors.initials: P
authors.lastname: Novota
authors.forename: Marianna
authors.initials: M
authors.lastname: Romzova
authors.forename: Pavlina
authors.initials: P
authors.lastname: Cejkova
authors.forename: Daniela
authors.initials: D
authors.lastname: Pinterova
authors.forename: Stepanka
authors.initials: S
authors.lastname: Pruhova
authors.forename: Ludmila
authors.initials: L
authors.lastname: Treslova
authors.forename: Michal
authors.initials: M
authors.lastname: Andel
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II