A case-control study on the association of common variants of CAPN10 gene and the risk of type 2 diabetes in an Iranian population.

Abstract

Calpain-10 is a ubiquitously expressed protease that serves as an intracellular calcium-dependent cysteine protease and is regarded to be one of the candidate genes for type 2 diabetes mellitus (T2DM). We aimed to identify the association of the common variants of this gene and the risk of T2DM in the Kurdish ethnic group of Iran. Study groups included 173 T2DM and 173 normoglycemic subjects. Genotyping was determined by PCR-RFLP. Genotypic and allelic frequencies were then evaluated. Data was analyzed using SPSS software. The allelic frequency of the A-allele of SNP-43 variant was significantly different (p = 0.01) between case and control groups (18% vs. 11%). The genotype frequencies for SNP-43 did not show any significant difference between case and control individuals. However, the dominant model of SNP-43 was found to be significantly associated with T2DM (OR = 1.75, 95% CI = 1.06 - 2.89, p < 0.029). The distribution and allele frequency of other SNPs (SNP-19 and -63) did not show any significant difference between the study groups. For SNP-43, fasting serum insulin (p = 0.043) and HOMA-IR (p = 0.026) were higher in the control subjects with the GA+AA genotype when compared with the GG genotype. Among the T2DM subjects, there was no significant difference in any of the clinical or biochemical parameters between the GG and GA+AA genotypes of SNP-43. Normoglycemic subjects carrying the 2R/3R+3R/3R genotypes of SNP-19 had significantly lower HDL-C (p = 0.034) as compared with those with the 2R/2R genotype. In T2DM subjects, no significant difference was found in any of the clinical or biochemical parameters between 2R/2R and 2R/3R+3R/3R genotypes. T2DM subjects carrying the CT+TT genotypes of SNP-63 variation had significantly higher LDL-C (p = 0.015) as compared with those with the CC genotype. In normoglycemic subjects, no significant difference was found in any of the clinical or biochemical parameters between CC and CT+TT genotypes. Our findings revealed that there is an association between the SNP-43, but not SNP-19 and -63, and T2DM in the Kurdish ethnic group of West Iran.