Association of the SNP-19 genotype 22 in the calpain-10 gene with elevated body mass index and hemoglobin A1c levels in Japanese

An association of variations in the calpain-10 gene (CAPN10) with type 2 diabetes was originally reported in Mexican Americans. However, some studies in other racial groups were contradictory. We studied the influence of genotypes and haplotype combinations (haplogenotypes) of CAPN10 on the metabolic traits in 286 Japanese subjects who visited a General Health Check-up Center. As for single nucleotide polymorphism (SNP)-19, subjects with genotype 22 had higher body mass index (BMI) and hemoglobin A(1c) (HbA(1c)) levels than those with genotypes 11 and 12 (p=0.003 and p=0.024, respectively). In SNP-63, subjects with genotype 11 had higher BMI and HbA(1c) levels than those with genotypes 12 and 22 (p=0.003 and p=0.045, respectively). Subjects who had genotype 22 at SNP-19 always had genotype 11 at SNP-63. Subjects with haplogenotype 121/121 had higher BMI levels (p=0.021) and tended to have higher HbA(1c) levels (p=0.08) than those with other haplogenotypes. All things considered, SNP-19 genotype 22, which was composed of haplogenotype 121/121 and 121/221, had highest significance level of association with elevated HbA(1c) levels. SNP-43 did not affect metabolic traits in our subjects. Subjects with haplogenotype 112/121 rather showed lower BMI and HbA(1c) levels (p=0.016 and p=0.008) than those with all other haplogenotypes. These results indicate the contribution of SNP-19 in CAPN10 to mild obesity and glucose intolerance in Japanese.