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Type 2 diabetes sus...
Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-06-07
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Springer Science and Business Media LLC,2014
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:ca562be0-396d-41fc-bc72-61a878c0da52
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https://lup.lub.lu.se/record/4659494URI
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https://doi.org/10.1007/s00125-014-3287-8DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-92900URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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.
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Sterner, MariaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-ms1
(author)
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Forsen, Tom
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Karajamaki, Annemari
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Rolandsson, OlovUmeå universitet,Allmänmedicin(Swepub:umu)olro0005
(author)
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Forsblom, Carol
(author)
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Groop, Per-Henrik
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Lahti, Kaj
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Nilsson, PeterLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)medf-pni
(author)
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Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr
(author)
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Tuomi, Tiinamaija
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Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:Diabetologia: Springer Science and Business Media LLC57:9, s. 1859-18681432-04280012-186X
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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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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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- MEDICAL AND HEALTH SCIENCES
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Diabetologia
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Lund University
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Umeå University