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  • Andersen, Mette (author)

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

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-06-07
  • Springer Science and Business Media LLC,2014

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:ca562be0-396d-41fc-bc72-61a878c0da52
  • https://lup.lub.lu.se/record/4659494URI
  • https://doi.org/10.1007/s00125-014-3287-8DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-92900URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • 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)
  • Forsen, Tom (author)
  • Karajamaki, Annemari (author)
  • Rolandsson, OlovUmeå universitet,Allmänmedicin(Swepub:umu)olro0005 (author)
  • Forsblom, Carol (author)
  • Groop, Per-Henrik (author)
  • Lahti, Kaj (author)
  • Nilsson, PeterLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)medf-pni (author)
  • 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)
  • Tuomi, Tiinamaija (author)
  • Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Diabetologia: Springer Science and Business Media LLC57:9, s. 1859-18681432-04280012-186X

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