Clinical characteristics, β‐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, β-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1α and HNF-4α genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies. Design and 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-1α and HNF-4α genes were performed. Results No differences were found in clinical presentation, metabolic control and β-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^β57 in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1α, Ala98Val; HNF-4α, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4α 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-1α and HNF-4α are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.