Calpain 10 Gene Polymorphism in Type 2 Diabetes Mellitus Patients in Gaza Strip

Abstract

Calpain-10 (CAPN10) is a member of a large family of intracellular proteases. The polymorphisms at CAPN10 gene have recently been associated with complex forms of type 2 diabetes mellitus (T2DM). It was shown in Mexican-Americans and other populations that variants of polymorphisms, single nucleotide polymorphism (SNP)-44, SNP-43, deletion/insertion (del/ins)-19, and SNP-63, of this gene influence susceptibility to T2DM. However, substantial differences were shown between ethnic groups in at risk alleles and haplotypes as well as in their attributable risk. Aim: To examine the role of CAPN10 SNPs -44, -43, -63, and del/ins-19 in genetic susceptibility to T2DM and to the levels of triglycerides and cholesterol in Gaza Strip. Methods: Ninety six individuals were examined: 48 T2DM patients and 48 control individuals. The groups were genotyped for CAPN10 SNP-44, SNP-43, SNP-63, and del/ins-19. Mutagenically separated polymerase chain reaction (MS-PCR) was used to examine SNP-44, del/ins-19 was examined by electrophoresis of the PCR product on agarose gel by size, while the restriction fragment length polymorphism (RFLP) method was used for SNP-43 and SNP-63. Results: There was no association between T2DM and allele frequencies of SNP-43, del/ins-19 and SNP-63. Distributions of genotypes, haplotypes and haplotypes combinations in the studied variants were not significantly different between the groups. However, there was evidence that the C-allele at SNP-44, plays a possible role in the susceptibility to T2DM (p=0.01). T2DM patients with G/A genotype were found to have higher cholesterol levels in comparison to those homozygous for allele 1 (G/G) in SNP-43. We found also that T2DM patients who are homozygous for del/ins-19 allele 2 have higher cholesterol levels in comparison to other genotypes. In addition, T2DM patients having the 121/221 haplotypes combination have higher serum cholesterol level than those with other haplotypes combinations. And that control subjects with haplotypes combination 111/121 have higher serum cholesterol level than those with other haplotypes combinations. Conclusion: The polymorphism SNP-44 at CAPN10 has an association with T2DM. CAPN10 also has an association with the levels of cholesterol in both T2DM patients and control individuals.