Endocrine Abstracts

Introduction: Genes involved in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM), dyslipidemia or hypertension are not disease specific, since clinically related disorders also share genetic components. These diseases cluster together in the Metabolic Syndrome, a generalized pathology with increased cardiovascular risk in which insulin resistance is considered a key feature. Cysteine protease Calpain-10 (CAPN10) has been associated with T2DM, polycystic ovary syndrome (PCOS), hypertension, hypercholesterolemia and increased body mass index (BMI). Calpain-5 gene is a CAPN10 homologue that lies in 11q13, a chromosomal region that has been linked to T2DM. We have analyzed the CAPN5 gene in several anthropometric and biochemical determinations related to metabolic syndrome.

Patients and methods: We have performed a QTL association analysis of four polymorphic variants of the CAPN5 gene in 606 individuals randomly chosen from a cross-sectional population-based epidemiological survey in the province of Segovia in Central Spain (Castille), recruited to investigate the prevalence of anthropometric and physiological parameters related to obesity and other components of the metabolic syndrome. Phenotype measures analyzed include BMI, waist circumference, blood pressure, fasting and 2h-glucose levels, fasting insulin, insulin resistance estimated as HOMA, total cholesterol, LDL-c, HDL-c and triglyceride levels. The study protocol was approved by the Ethics Committee of the reference Hospital.

Results: Genotype analysis was significant for BMI (P≤0.041), diastolic blood pressure (P=0.015) and HDL-cholesterol levels (P=0.025). Different haplotypes were also associated with BMI (0.022≤P≤0.043), diastolic blood pressure (0.0005≤P≤0.010) and total cholesterol levels (0.001≤P≤0.048). In accordance with the quantitative haplotype analysis, the AACA haplotype is more prevalent in individuals with obesity (P=0.031), obesity with hypertension (P=0.023) and metabolic syndrome (P=0.029).

Conclusions: Our results suggest that Calpain-5 gene variants could contribute to the development of obesity and related cardiovascular risk factors such as hypertension and dyslipidemia in the context of metabolic syndrome.