TY - JOUR
T1 - Association of the calpain-10 gene with type 2 diabetes in Europeans
T2 - Results of pooled and meta-analyses
AU - Tsuchiya, Takafumi
AU - Schwarz, Peter E H
AU - Bosque-Plata, Laura del
AU - Geoffrey Hayes, M.
AU - Dina, Christian
AU - Froguel, Philippe
AU - Wayne Towers, G.
AU - Fischer, Sabine
AU - Temelkova-Kurktschiev, Theodora
AU - Rietzsch, Hannes
AU - Graessler, Juergen
AU - Vcelák, Josef
AU - Palyzová, Daniela
AU - Selisko, Thomas
AU - Bendlová, Bela
AU - Schulze, Jan
AU - Julius, Ulrich
AU - Hanefeld, Markolf
AU - Weedon, Michael N.
AU - Evans, Julie C.
AU - Frayling, Timothy M.
AU - Hattersley, Andrew T.
AU - Orho-Melander, Marju
AU - Groop, Leif
AU - Malecki, Maciej T.
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Fingerlin, Tasha E.
AU - Boehnke, Michael
AU - Hanis, Craig L.
AU - Cox, Nancy J.
AU - Bell, Graeme I.
N1 - Funding Information:
This study was supported in part by U.S. Public Health Service (Grants DK-20595, -47486, -47487 and -55889), a grant from the Technical University Dresden (Med Drive), a grant from the Czech government (IGA MH CR NR/7809-5), and a gift from the Kovler Family Foundation. M.G.H. was supported by a Mentor-based Fellowship from the American Diabetes Association. G.W.T. was supported by a postdoctoral fellowship from the North-West University (Potchefstroom Campus).
PY - 2006/9
Y1 - 2006/9
N2 - 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 (CI), 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.
AB - 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 (CI), 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.
KW - Association study
KW - Calpain-10
KW - Diabetes mellitus
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U2 - 10.1016/j.ymgme.2006.05.013
DO - 10.1016/j.ymgme.2006.05.013
M3 - Article
C2 - 16837224
AN - SCOPUS:33746943663
SN - 1096-7192
VL - 89
SP - 174
EP - 184
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -
