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

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Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes. / Andersen, Mette; Sterner, Maria; Forsen, Tom; Karajamaki, Annemari; Rolandsson, Olov; Forsblom, Carol; Groop, Per-Henrik; Lahti, Kaj; Nilsson, Peter; Groop, Leif; Tuomi, Tiinamaija.

In: Diabetologia, Vol. 57, No. 9, 2014, p. 1859-1868.

Research output: Contribution to journalArticle

Harvard

Andersen, M, Sterner, M, Forsen, T, Karajamaki, A, Rolandsson, O, Forsblom, C, Groop, P-H, Lahti, K, Nilsson, P, Groop, L & Tuomi, T 2014, 'Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes', Diabetologia, vol. 57, no. 9, pp. 1859-1868. https://doi.org/10.1007/s00125-014-3287-8

APA

Andersen, M., Sterner, M., Forsen, T., Karajamaki, A., Rolandsson, O., Forsblom, C., Groop, P-H., Lahti, K., Nilsson, P., Groop, L., & Tuomi, T. (2014). Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes. Diabetologia, 57(9), 1859-1868. https://doi.org/10.1007/s00125-014-3287-8

CBE

Andersen M, Sterner M, Forsen T, Karajamaki A, Rolandsson O, Forsblom C, Groop P-H, Lahti K, Nilsson P, Groop L, Tuomi T. 2014. Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes. Diabetologia. 57(9):1859-1868. https://doi.org/10.1007/s00125-014-3287-8

MLA

Vancouver

Andersen M, Sterner M, Forsen T, Karajamaki A, Rolandsson O, Forsblom C et al. Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes. Diabetologia. 2014;57(9):1859-1868. https://doi.org/10.1007/s00125-014-3287-8

Author

Andersen, Mette ; Sterner, Maria ; Forsen, Tom ; Karajamaki, Annemari ; Rolandsson, Olov ; Forsblom, Carol ; Groop, Per-Henrik ; Lahti, Kaj ; Nilsson, Peter ; Groop, Leif ; Tuomi, Tiinamaija. / Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes. In: Diabetologia. 2014 ; Vol. 57, No. 9. pp. 1859-1868.

RIS

TY - JOUR

T1 - Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes

AU - Andersen, Mette

AU - Sterner, Maria

AU - Forsen, Tom

AU - Karajamaki, Annemari

AU - Rolandsson, Olov

AU - Forsblom, Carol

AU - Groop, Per-Henrik

AU - Lahti, Kaj

AU - Nilsson, Peter

AU - Groop, Leif

AU - Tuomi, Tiinamaija

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Adult-onset type 1 diabetes

KW - GADA

KW - GAD autoantibodies

KW - Genetics

KW - HNF1A

KW - LADA

KW - Latent autoimmune diabetes in adults

KW - MTNR1B

KW - TCF7L2

KW - ZMIZ1

U2 - 10.1007/s00125-014-3287-8

DO - 10.1007/s00125-014-3287-8

M3 - Article

VL - 57

SP - 1859

EP - 1868

JO - Diabetologia

JF - Diabetologia

SN - 1432-0428

IS - 9

ER -