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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.