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

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.