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Type 2 diabetes sus...
Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes
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Andersen, Mette (author)
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- Sterner, Maria (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Forsen, Tom (author)
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Karajamaki, Annemari (author)
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- Rolandsson, Olov (author)
- Umeå universitet,Allmänmedicin
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Forsblom, Carol (author)
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Groop, Per-Henrik (author)
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Lahti, Kaj (author)
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- Nilsson, Peter (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Tuomi, Tiinamaija (author)
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(creator_code:org_t)
- 2014-06-07
- 2014
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 57:9, s. 1859-1868
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Adult-onset type 1 diabetes
- GADA
- GAD autoantibodies
- Genetics
- HNF1A
- LADA
- Latent autoimmune diabetes in adults
- MTNR1B
- TCF7L2
- ZMIZ1
- Adult-onset type 1 diabetes
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Andersen, Mette
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Sterner, Maria
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Forsen, Tom
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Karajamaki, Anne ...
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Rolandsson, Olov
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Forsblom, Carol
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show more...
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Groop, Per-Henri ...
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Lahti, Kaj
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Nilsson, Peter
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Groop, Leif
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Tuomi, Tiinamaij ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Lund University
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Umeå University