Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes
(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)
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https://lup.lub.lu.se/record/4659494
- author
- organization
- publishing date
- 2014
- 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
- 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
- 2016-04-01 09:55:41
- date last changed
- 2024-02-21 00:02:34
@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}},
keywords = {{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}},
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}},
doi = {{10.1007/s00125-014-3287-8}},
volume = {{57}},
year = {{2014}},
}