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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Association of the calpain-10 gene with type 2 diabetes in Europeans: Results of pooled and meta-analyses

Author

  • Takafumi Tsuchiya
  • Peter E. H. Schwarz
  • Laura del Bosque-Plata
  • M. Geoffrey Hayes
  • Christian Dina
  • Philippe Froguel
  • G. Wayne Towers
  • Sabine Fischer
  • Theodora Temelkova-Kurktschiev
  • Hannes Rietzsch
  • Juergen Graessler
  • Josef Vcelak
  • Daniela Palyzova
  • Thomas Selisko
  • Bela Bendlova
  • Jan Schulze
  • Ulrich Julius
  • Markolf Hanefeld
  • Michael N. Weedon
  • Julie C. Evans
  • Timothy M. Frayling
  • Andrew T. Hattersley
  • Marju Orho-Melander
  • Leif Groop
  • Maciej T. Malecki
  • Torben Hansen
  • Oluf Pedersen
  • Tasha E. Fingerlin
  • Michael Boehnke
  • Craig L. Hanis
  • Nancy J. Cox
  • Graeme I. Bell

Summary, in English

We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR) = 1.11 (95% confidence interval (0), 1.02-1.20), P = 0.01). Two haplotype combinations were associated with increased risk of T2D) (1-2-1/1-2-1, OR = 1.20 (1.03-1.41), P = 0.02; and 1-1-2/1-2-1, OR = 1.26 (1.01-1.59), P = 0.04) and one with decreased risk (1-1-1/2-2-1, OR = 0.86 (0.75-0.99), P = 0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR = 1.25 (1.05-1.50), P = 0.01). However, there was evidence for heterogeneity with respect to this effect (P = 0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P = 0.89) and strengthened the evidence for association with T2D) in both the pooled (SNP-43*G, OR = 1.19 (1.07-1.32), P = 0.001; 1-2-1/1-2-1 haplogenotype, OR = 1.46 (1.19-1.78), P = 0.0003; 1-1-2/1-2-1 haplogenotype, OR = 1.52 (1.12-2.06), P = 0.007; and 1-1-1/2-2-1 haplogenotype, OR = 0.83 (0.70-0.99), P = 0.03) and the meta-analysis (SNP-43*G, OR = 1.18 (1.05-1.32), P = 0.005; 1-2-1/1-2-1 haplogenotype, OR = 1.68 (1.33-2.11), P = 0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans. (c) 2006 Elsevier Inc. All rights reserved.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

2006

Language

English

Pages

174-184

Publication/Series

Molecular Genetics and Metabolism

Volume

89

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • diabetes mellitus
  • calpain-10
  • association study

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1096-7192