Genetic Similarities Between Latent Autoimmune Diabetes in Adults, Type 1 Diabetes, and Type 2 Diabetes

  1. Camilla Cervin1,
  2. Valeriya Lyssenko1,
  3. Ekaterine Bakhtadze1,
  4. Eero Lindholm1,
  5. Peter Nilsson2,
  6. Tiinamaija Tuomi34,
  7. Corrado M. Cilio5 and
  8. Leif Groop13
  1. 1Department of Clinical Sciences—Diabetes & Endocrinology, Clinical Research Center, Malmö University Hospital, Lund University, Malmö, Sweden
  2. 2Department of Medicine, Malmö University Hospital, Lund University, Malmö, Sweden
  3. 3Department of Medicine, Helsinki University Central Hospital, and Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland
  4. 4Folkhalsan Research Centre, Helsinki, Finland
  5. 5Department of Clinical Sciences, Cellular Autoimmunity Unit, Clinical Research Center, Malmö University Hospital, Lund University, Malmö, Sweden
  1. Corresponding author: Leif Groop, Department of Clinical Sciences—Diabetes & Endocrinology, Clinical Research Center, Malmö University Hospital, Lund University, S-205 02 Malmö, Sweden. E-mail: leif.groop{at}med.lu.se

Abstract

OBJECTIVE—Latent autoimmune diabetes in adults (LADA) is often considered a slowly progressing subtype of type 1 diabetes, although the clinical picture more resembles type 2 diabetes. One way to improve classification is to study whether LADA shares genetic features with type 1 and/or type 2 diabetes.

RESEARCH DESIGN AND METHODS—To accomplish this, we studied whether LADA shares variation in the HLA locus or INS VNTR and PTPN22 genes with type 1 diabetes or the TCF7L2 gene with type 2 diabetes in 361 LADA, 718 type 1 diabetic, and 1,676 type 2 diabetic patients, as well as 1,704 healthy control subjects from Sweden and Finland.

RESULTS—LADA subjects showed, compared with type 2 diabetic patients, increased frequency of risk for the HLA-DQB1 *0201/*0302 genotype (27 vs. 6.9%; P < 1 × 10−6), with similar frequency as with type 1 diabetes (36%). In addition, LADA subjects showed higher frequencies of protective HLA-DQB1 *0602(3)/X than type 1 diabetic patients (8.1 vs. 3.2%, P = 0.003). The AA genotype of rs689, referring to the class I allele in the INS VNTR, as well as the CT/TT genotypes of rs2476601 in the PTPN22 gene, were increased both in type 1 diabetic (P = 3 × 10−14 and P = 1 × 10−10, respectively) and LADA (P = 0.001 and P = 0.002) subjects compared with control subjects. Notably, the frequency of the type 2 diabetes–associated CT/TT genotypes of rs7903146 in the TCF7L2 were increased in LADA subjects (52.8%; P = 0.03), to the same extent as in type 2 diabetic subjects (54.1%, P = 3 × 10−7), compared with control subjects (44.8%) and type 1 diabetic subjects (43.3%).

CONCLUSIONS—LADA shares genetic features with both type 1 (HLA, INS VNTR, and PTPN22) and type 2 (TCF7L2) diabetes, which justifies considering LADA as an admixture of the two major types of diabetes.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 29 February 2008. DOI: 10.2337/db07-0299.

    Leif Groop has been a consultant for and has served on advisory boards of sanofi-aventis, Bristol-Meyers Squibb, GlaxoSmithKline, and F. Hoffmann-La Roche.

    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.

    See accompanying commentary on p. 1160.

    • Accepted February 14, 2008.
    • Received March 2, 2007.
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  1. Diabetes vol. 57 no. 5 1433-1437
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