Abstract

BackgroundGenetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D).MethodsWe examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.ResultsEnrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls.ConclusionsCAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians.

Highlights

  • Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D)

  • Of the diabetes-related genes, fine mapping and positional cloning suggested that the calpain-10 (CAPN10) gene might serve as an important T2D susceptibility gene [3,4]

  • Patients and control subjects were matched for gender, age, ethnic origin, and geographical origin; significant differences were noted between the two groups with regards to Body Mass Index (BMI) (P < 0.001), blood pressure (P < 0.001), lipid profile (P < 0.001), urea (P < 0.001), and fasting glucose (P < 0.001) and HbA1c levels (P < 0.001)

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Summary

Introduction

Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D). Several case control and association studies indicated that polymorphisms in CAPN10 are associated with the development of T2D and insulin resistance, more so in obese patients with an earlier age of disease onset [6,8,9,10].

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