2009/10/15 by Elin Pettersen, Frank Skorpen, Kirsti Kvaløy +2 · 87 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Immunology and Microbiology · #Diabetes and associated disorders #Pancreatic function and diabetes #T-cell and B-cell Immunology #Type 2 diabetes #Single-nucleotide polymorphism #Medicine #Haplotype #Autoimmune diabetes #Type 1 diabetes #Diabetes mellitus #Human leukocyte antigen #Population #Genotype #Internal medicine #Immunology #Endocrinology #Genetics #Biology #Gene #Antigen
paper · pdf · doi:10.2337/db09-0923
published in Diabetes 59(1), 302-310 (American Diabetes Association)
openalex publication_date 2009/10/15 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/31
OBJECTIVE: Previous studies have indicated that the latent autoimmune diabetes in adults (LADA) phenotype is heterogeneous and that LADA patients share features of type 1 and type 2 diabetes in various proportions. We tested for association of known type 1 and type 2 diabetes susceptibility genes in LADA subjects and analyzed relationships to a marker of autoimmune activity (titers of anti-GAD) and a phenotypic risk factor of type 2 diabetes (BMI). RESEARCH DESIGN AND METHODS: Data were assembled from the Nord-Trøndelag Health Study (HUNT) study, which comprises the adult population of an entire county in Norway. We genotyped 60 single nucleotide polymorphisms (SNPs) known to be associated with type 1 or type 2 diabetes, including 14 tag SNPs used for HLA haplotyping in 120 type 1 diabetic, 126 LADA, and 1,090 type 2 diabetic patients and 1,503 age- and sex-matched nondiabetic subjects. RESULTS: The majority of the strongly associated HLA haplotypes for type 1 diabetes were significantly associated with LADA in general, but mainly with high anti-GAD LADA patients. Two distinct HLA haplotypes were associated only with LADA and mainly in low anti-GAD LADA patients. There were no associations of non-HLA type 1 diabetes loci with LADA. Of type 2 diabetes-associated genes, the CC/CT genotypes of rs7961581 (TSPAN8) and the obesity-linked AA/AC genotypes of rs8050136 (FTO) were associated with LADA in general, but mainly in low anti-GAD LADA patients (P = 0.004 and P = 0.004, respectively). CONCLUSIONS: Genetic heterogeneity in LADA is linked to various degrees of autoimmune activity and may be partly distinct from both type 1 and type 2 diabetes.