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

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• 作者：Mette K. Andersen (1) (2) (3) r> Maria Sterner (4) r> Tom Forsén (5) r> Annemari K?r?j?m?ki (6) (7) r> Olov Rolandsson (8) r> Carol Forsblom (1) (2) (9) r> Per-Henrik Groop (1) (10) (2) (9) r> Kaj Lahti (6) r> Peter M. Nilsson (11) r> Leif Groop (3) (4) r> Tiinamaija Tuomi (1) (12) (2) r>
• 关键词：Adult ; onset type 1 diabetes ; GADA ; GAD autoantibodies ; Genetics ; HNF1A ; LADA ; Latent autoimmune diabetes in adults ; MTNR1B ; TCF7L2 ; ZMIZ1
• 刊名：Diabetologia
• 出版年：2014
• 出版时间：September 2014
• 年：2014
• 卷：57
• 期：9
• 页码：1859-1868
• 全文大小：472 KB
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• 作者单位：Mette K. Andersen (1) (2) (3) r> Maria Sterner (4) r> Tom Forsén (5) r> Annemari K?r?j?m?ki (6) (7) r> Olov Rolandsson (8) r> Carol Forsblom (1) (2) (9) r> Per-Henrik Groop (1) (10) (2) (9) r> Kaj Lahti (6) r> Peter M. Nilsson (11) r> Leif Groop (3) (4) r> Tiinamaija Tuomi (1) (12) (2) r>r>1. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland r> 2. Folkh?lsan Research Center, HUS, 00029, Helsinki, Finland r> 3. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland r> 4. Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malm?, Sweden r> 5. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland r> 6. Vasa Health Care Center, Vasa, Finland r> 7. Department of Primary Health Care, Vasa Central Hospital, Vasa, Finland r> 8. Department of Public Health and Clinical Medicine, Family Medicine, Ume? University, Ume?, Sweden r> 9. Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland r> 10. Baker IDI Heart and Diabetes Institute, Melbourne, Australia r> 11. Department of Clinical Sciences, Division of Medicine, Lund University, Malm?, Sweden r> 12. Department of Medicine, Helsinki University Hospital, Helsinki, Finland r>
• ISSN：1432-0428

文摘

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--11) or type 1 diabetes (n--06), all diagnosed after the age of 35?years, as well as in non-diabetic control individuals 40?years or older (n--,002). Results Variants in the ZMIZ1 (rs12571751, p--.1?×-0?) and TCF7L2 (rs7903146, p--.8?×-0?) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p--.0012), HHEX (rs1111875, p--.0024 in Finns) and MTNR1B (rs10830963, p--.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--.5?×-0? in Finns), TP53INP1 (rs896854, p--.005), CDKAL1 (rs7756992, p--.0?×-0?; rs7754840, p--.8?×-0?) and PROX1 (rs340874, p--.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p--.2?×-0?) and HNF1A (rs2650000, p--.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.