title: Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses.
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 (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.
authors.affiliation: Departments of Medicine and Human Genetics, The University of Chicago, 5841 S. Maryland Ave., MC1027, Chicago, IL 60637, USA.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Peter E H
authors.initials: PE
authors.lastname: Schwarz
authors.forename: Laura Del
authors.initials: LD
authors.lastname: Bosque-Plata
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authors.lastname: Geoffrey Hayes
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Philippe
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authors.lastname: Froguel
authors.forename: G
authors.initials: G
authors.lastname: Wayne Towers
authors.forename: Sabine
authors.initials: S
authors.lastname: Fischer
authors.forename: Theodora
authors.initials: T
authors.lastname: Temelkova-Kurktschiev
authors.forename: Hannes
authors.initials: H
authors.lastname: Rietzsch
authors.forename: Juergen
authors.initials: J
authors.lastname: Graessler
authors.forename: Josef
authors.initials: J
authors.lastname: Vcelák
authors.forename: Daniela
authors.initials: D
authors.lastname: Palyzová
authors.forename: Thomas
authors.initials: T
authors.lastname: Selisko
authors.forename: Bela
authors.initials: B
authors.lastname: Bendlová
authors.forename: Jan
authors.initials: J
authors.lastname: Schulze
authors.forename: Ulrich
authors.initials: U
authors.lastname: Julius
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Julie C
authors.initials: JC
authors.lastname: Evans
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
mesh_terms: D002154:Calpain / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D002154:Calpain; C415197:calpain 10