Variants within the calpain-10 gene and relationships with type 2 diabetes (T2DM) and T2DM-related traits among Tunisian Arabs

• Published in: Diabetes & metabolism 2010-11, Vol.36 (5), p.357-362
• Main Authors: Ezzidi, I, Mtiraoui, N, Nemr, R, Kacem, M, Al-Khateeb, G.M, Mahjoub, T, Almawi, W.Y
• Format: Article
• Language: English
• Subjects: Aged; Arabs - genetics; Biological and medical sciences; Blood Glucose - analysis; Body Mass Index; Calpain - genetics; Calpain-10; Calpaine-10; Cholesterol, HDL - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabète de type 2; Diplotypes; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Internal Medicine; Linkage stdy; Male; Medical sciences; Middle Aged; Obesity - genetics; Overweight - genetics; Polymerase Chain Reaction; Polymorphism; Polymorphism, Genetic - genetics; Polymorphism, Restriction Fragment Length; Polymorphismes; Tunisia; Tunisian; Tunisiens; Type 2 diabetes; Études d’association
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2010.03.005

Abstract Background Common variations in the calpain 10 (CAPN10) gene variants UCSNP-43, UCSNP-19 and UCSNP-63, and the 112/121 diplotype, are associated with an increased risk of type 2 diabetes (T2DM) and T2DM-related traits. Methods The association of UCSNP-43, -19 and -63 CAPN10 SNPs with T2DM was assessed in 917 Tunisian T2DM patients and 748 ethnically matched non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP. Results Significant differences in UCSNP-19 MAF, but not UCSNP-43 or -63, and genotype distribution were seen between patients and controls. Heterogeneity in UCSNP-19, but not UCSNP-43 and -63, genotype distribution was noted according to geographical origin. Obesity was associated with UCSNP-19, while raised fasting glucose was associated with UCSNP-63, and increased HDL was associated with UCSNP-43. Enrichment of homozygous UCSNP-19 2/2 was seen in overweight and obese compared with lean patients; logistic-regression analyses demonstrated a positive association of the 2/2 genotype with overweight [ P = 0.003; OR (95% CI) = 2.07 (1.28–3.33)] and obese [ P = 0.021; OR (95% CI) = 1.83 (1.10–3.07)] patients. Of the six CAPN10 haplotypes identified, significant enrichment of only haplotype 111 was seen in T2DM patients [ Pc = 0.034; OR (95% CI) = 1.22 (1.06–1.41)], while the frequency of all identified CAPN10 diplotypes, including the high-risk 112/121, was comparable between patients and controls. Conclusion While CAPN10 UCSNP-19 SNP and haplotype 111 contribute to the risk of T2DM in Tunisian subjects, no significant association between CAPN10 diplotypes and T2DM was demonstrated.