Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Lepola, Mette Andersen
  • Maria Sterner
  • Tom Forsén
  • Annemari Käräjämäki
  • Olov Rolandsson
  • Carol Forsblom
  • Per Henrik Groop
  • Kaj Lahti
  • Peter M. Nilsson
  • Leif Groop
  • Tiinamaija Tuomi

Aims/hypothesis: Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA). Methods: We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n = 911) or type 1 diabetes (n = 406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n = 4,002). Results: Variants in the ZMIZ1 (rs12571751, p = 4.1 × 10-5) and TCF7L2 (rs7903146, p = 5.8 × 10-4) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p = 0.0012), HHEX (rs1111875, p = 0.0024 in Finns) and MTNR1B (rs10830963, p = 0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p = 9.5 × 10-4 in Finns), TP53INP1 (rs896854, p = 0.005), CDKAL1 (rs7756992, p = 7.0 × 10 -4; rs7754840, p = 8.8 × 10-4) and PROX1 (rs340874, p = 0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p = 3.2 × 10-6) and HNF1A (rs2650000, p = 0.0012). Conclusions/ interpretation: LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes.

Udgave nummer9
Sider (fra-til)1859-1868
Antal sider10
StatusUdgivet - 1 jan. 2014

ID: 200858252