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

Tsuchiya, Takafumi ; Schwarz, Peter E. H. ; del Bosque-Plata, Laura ; Hayes, M. Geoffrey ; Dina, Christian ; Froguel, Philippe ; Towers, G. Wayne ; Fischer, Sabine ; Temelkova-Kurktschiev, Theodora and Rietzsch, Hannes , et al. (2006) In Molecular Genetics and Metabolism 89(1-2). p.174-184
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diabetes mellitus, calpain-10, association study
in
Molecular Genetics and Metabolism
volume
89
issue
1-2
pages
174 - 184
publisher
Elsevier
external identifiers
  • wos:000240532500024
  • scopus:33746943663
  • pmid:16837224
ISSN
1096-7192
DOI
10.1016/j.ymgme.2006.05.013
language
English
LU publication?
yes
id
d9b44a34-dae2-479e-99ba-a6e7735a3914 (old id 392952)
date added to LUP
2016-04-01 12:01:48
date last changed
2020-12-15 03:41:53
@article{d9b44a34-dae2-479e-99ba-a6e7735a3914,
  abstract     = {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.},
  author       = {Tsuchiya, Takafumi and Schwarz, Peter E. H. and del Bosque-Plata, Laura and Hayes, M. Geoffrey and Dina, Christian and Froguel, Philippe and Towers, G. Wayne and Fischer, Sabine and Temelkova-Kurktschiev, Theodora and Rietzsch, Hannes and Graessler, Juergen and Vcelak, Josef and Palyzova, Daniela and Selisko, Thomas and Bendlova, Bela and Schulze, Jan and Julius, Ulrich and Hanefeld, Markolf and Weedon, Michael N. and Evans, Julie C. and Frayling, Timothy M. and Hattersley, Andrew T. and Orho-Melander, Marju and Groop, Leif and Malecki, Maciej T. and Hansen, Torben and Pedersen, Oluf and Fingerlin, Tasha E. and Boehnke, Michael and Hanis, Craig L. and Cox, Nancy J. and Bell, Graeme I.},
  issn         = {1096-7192},
  language     = {eng},
  number       = {1-2},
  pages        = {174--184},
  publisher    = {Elsevier},
  series       = {Molecular Genetics and Metabolism},
  title        = {Association of the calpain-10 gene with type 2 diabetes in Europeans: Results of pooled and meta-analyses},
  url          = {http://dx.doi.org/10.1016/j.ymgme.2006.05.013},
  doi          = {10.1016/j.ymgme.2006.05.013},
  volume       = {89},
  year         = {2006},
}