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 K.; Sterner, Maria; Forsén, Tom; Käräjämäki, Annemari; Rolandsson, Olov; Forsblom, Carol; Groop, Per Henrik; Lahti, Kaj; Nilsson, Peter M.; Groop, Leif; Tuomi, Tiinamaija.
In: Diabetologia, Vol. 57, No. 9, 01.01.2014, p. 1859-1868.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes
AU - Andersen, Mette K.
AU - Sterner, Maria
AU - Forsén, Tom
AU - Käräjämäki, Annemari
AU - Rolandsson, Olov
AU - Forsblom, Carol
AU - Groop, Per Henrik
AU - Lahti, Kaj
AU - Nilsson, Peter M.
AU - Groop, Leif
AU - Tuomi, Tiinamaija
PY - 2014/1/1
Y1 - 2014/1/1
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 × 10-5) and TCF7L2 (rs7903146, p = 5.8 × 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 × 10-4 in Finns), TP53INP1 (rs896854, p = 0.005), CDKAL1 (rs7756992, p = 7.0 × 10 -4; rs7754840, p = 8.8 × 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 × 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 × 10-5) and TCF7L2 (rs7903146, p = 5.8 × 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 × 10-4 in Finns), TP53INP1 (rs896854, p = 0.005), CDKAL1 (rs7756992, p = 7.0 × 10 -4; rs7754840, p = 8.8 × 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 × 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 - GAD autoantibodies
KW - GADA
KW - Genetics
KW - HNF1A
KW - LADA
KW - Latent autoimmune diabetes in adults
KW - MTNR1B
KW - TCF7L2
KW - ZMIZ1
UR - http://www.scopus.com/inward/record.url?scp=84905569151&partnerID=8YFLogxK
U2 - 10.1007/s00125-014-3287-8
DO - 10.1007/s00125-014-3287-8
M3 - Journal article
C2 - 24906951
AN - SCOPUS:84905569151
VL - 57
SP - 1859
EP - 1868
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 9
ER -
ID: 200858252