title: Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies.
abstract: OBJECTIVE
  To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies.
  
  
  METHODS
  Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed.
  
  
  RESULTS
  No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.
authors.affiliation: Endocrinology and Diabetes Unit, IDIBAPS, Hospital Clínic i Universitari, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Aguilera
authors.forename: R
authors.initials: R
authors.lastname: Casamitjana
authors.forename: G
authors.initials: G
authors.lastname: Ercilla
authors.forename: J
authors.initials: J
authors.lastname: Oriola
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
authors.forename: R
authors.initials: R
authors.lastname: Gomis
authors.forename: I
authors.initials: I
authors.lastname: Conget
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005802:Genes, MHC Class II / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D006650:Histocompatibility Testing; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001323:Autoantibodies; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1