Advanced

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

Andersen, Mette; Sterner, Maria LU ; Forsen, Tom; Karajamaki, Annemari; Rolandsson, Olov; Forsblom, Carol; Groop, Per-Henrik; Lahti, Kaj; Nilsson, Peter LU and Groop, Leif LU , et al. (2014) In Diabetologia 57(9). p.1859-1868
Abstract
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... (More)
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 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 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 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 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 x 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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adult-onset type 1 diabetes, GADA, GAD autoantibodies, Genetics, HNF1A, LADA, Latent autoimmune diabetes in adults, MTNR1B, TCF7L2, ZMIZ1
in
Diabetologia
volume
57
issue
9
pages
1859 - 1868
publisher
Springer Verlag
external identifiers
  • wos:000340050800016
  • scopus:84905569151
ISSN
1432-0428
DOI
10.1007/s00125-014-3287-8
language
English
LU publication?
yes
id
ca562be0-396d-41fc-bc72-61a878c0da52 (old id 4659494)
date added to LUP
2014-10-01 07:23:56
date last changed
2017-10-22 03:02:39
@article{ca562be0-396d-41fc-bc72-61a878c0da52,
  abstract     = {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 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 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 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 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 x 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.},
  author       = {Andersen, Mette and Sterner, Maria and Forsen, Tom and Karajamaki, Annemari and Rolandsson, Olov and Forsblom, Carol and Groop, Per-Henrik and Lahti, Kaj and Nilsson, Peter and Groop, Leif and Tuomi, Tiinamaija},
  issn         = {1432-0428},
  keyword      = {Adult-onset type 1 diabetes,GADA,GAD autoantibodies,Genetics,HNF1A,LADA,Latent autoimmune diabetes in adults,MTNR1B,TCF7L2,ZMIZ1},
  language     = {eng},
  number       = {9},
  pages        = {1859--1868},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-014-3287-8},
  volume       = {57},
  year         = {2014},
}