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Genetic Heterogeneity in Latent Autoimmune Diabetes Is Linked to Various Degrees of Autoimmune Activity

Results From the Nord-Trøndelag Health Study

  1. Elin Pettersen1,
  2. Frank Skorpen2,
  3. Kirsti Kvaløy3,
  4. Kristian Midthjell4 and
  5. Valdemar Grill1,5
  1. 1Department of Cancer Research and Molecular Medicine, Faculty of Medicine, The Norwegian University of Science and Technology, Trondheim, Norway;
  2. 2Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, The Norwegian University of Science and Technology, Trondheim, Norway;
  3. 3HUNT Research Centre, Department of Public Health and General Practice, Faculty of Medicine, The Norwegian University of Science and Technology, Levanger, Norway;
  4. 4HUNT Research Centre, Department of Public Health and General Practice, Faculty of Medicine, The Norwegian University of Science and Technology, Verdal, Norway;
  5. 5Department of Endocrinology, St. Olav University Hospital, Trondheim, Norway.
  1. Corresponding author: Elin Pettersen, elin.pettersen{at}ntnu.no.

Abstract

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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received June 23, 2009.
    • Accepted September 16, 2009.
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This Article

  1. Published online before print October 15, 2009, doi: 10.2337/db09-0923 Diabetes January 2010 vol. 59 no. 1 302-310
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