Variation in CAPN10 in relation to type 2 diabetes, obesity and quantitative metabolic traits: Studies in 6018 whites

The first type 2 diabetes (T2D) gene to be identified in a genome wide scan followed by positional cloning was CAPN10 encoding the cysteine protease calpain-10. Subsequently, a large number of studies have investigated variation in CAPN10 in relation to T2D. Two CAPN10 single nucleotide polymorphisms (SNPs), the SNP43 (rs3792267) and the SNP44 (rs2975760), have been associated with T2D in some, but not all studies conducted in a wide range of ethnicities. We investigated the two SNPs for association with T2D in a relatively large, homogenous population of Danish whites (n = 1359 T2D cases, n = 4659 normoglycemic and glucose-tolerant control subjects), however, no significant associations of the SNP43 or the SNP44 variant with T2D were found. Neither were the two variants associated with obesity, and no association of either variant with diabetes-related quantitative traits was found in a study involving a population-based sample of 5698 middle-aged subjects. Meta-analyses, however, of the present and previously published studies involving 15,368 (SNP43) or 13,628 (SNP44) subjects yielded odds ratios of 1.09 (95% CI 1.02-1.16, p = 0.007) and 1.15 (1.07-1.23, p = 0.0002), respectively, for association with T2D. In conclusion, in a relatively large study sample of whites we found no consistent evidence of association of the CAPN10 SNP43 or SNP44 with T2D, obesity, or related quantitative traits, although meta-analyses of these two CAPN10 SNPs demonstrated an association with T2D.