Abstract
BackgroundGenes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific, since clinically related disorders also share genetic components. Cysteine protease Calpain 10 (CAPN10) has been associated with T2DM, hypertension, hypercholesterolemia, increased body mass index (BMI) and polycystic ovary syndrome (PCOS), a reproductive disorder of women in which isunlin resistance seems to play a pathogenic role. The calpain 5 gene (CAPN5) encodes a protein homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group. In this new study, we have analysed the association of four CAPN5 gene variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A) with several cardiovascular risk factors related to metabolic syndrome in general population.MethodsAnthropometric measurements, blood pressure, insulin, glucose and lipid profiles were determined 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. Genotypes at the four polymorphic loci in CAPN5 gene were detected by polymerase chain reaction (PCR).ResultsGenotype association analysis was significant for BMI (p ≤ 0.041), diastolic blood pressure (p = 0.015) and HDL-cholesterol levels (p = 0.025). Different CAPN5 haplotypes were also associated with diastolic blood pressure (DBP) (0.0005 ≤ p ≤ 0.006) and total cholesterol levels (0.001 ≤ p ≤ 0.029). In addition, the AACA haplotype, over-represented in obese individuals, is also more frequent in individuals with metabolic syndrome defined by ATPIII criteria (p = 0.029).ConclusionAs its homologue CAPN10, CAPN5 seems to influence traits related to increased risk for cardiovascular diseases. Our results also may suggest CAPN5 as a candidate gene for metabolic syndrome.
Highlights
Genes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific, since clinically related disorders share genetic components
Calpain 10 (CAPN10), calpain 5 (CAPN5) and calpain 6 (CAPN6) proteins belong to the non-EF-hand subfamily that lacks these calcium-binding motifs; these calpains differ from the remaining members of this subfamily in the presence of a T-domain homologous to C.elegans TRA-3, a protein implicated in the sexual determination of the hermaphrodite worm [4,5]
The FEM1A gene maps to chromosome 19p13.3, a region linked to polycystic ovary syndrome (PCOS), a common endocrine disorder of women of reproductive age, characterized by chronic anovulation, infertility, hyperandrogenemia and frequently, insulin resistance resulting in an increased prevalence of obesity, cardiovascular disease (CVD) and T2DM, reason why PCOS is consider a phenotype closely related to metabolic syndrome
Summary
Genes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific, since clinically related disorders share genetic components. Factors that increase the risk of cardiovascular disease (CVD) include obesity, dyslipidemia, glucose intolerance, type 2 diabetes mellitus (T2DM) and hypertension. When these factors cluster in an individual is called metabolic syndrome (MS), a complex disorder characterized by impaired glucose metabolism, dyslipidemia, hypertension and obesity [1]. The FEM1A gene maps to chromosome 19p13.3, a region linked to polycystic ovary syndrome (PCOS), a common endocrine disorder of women of reproductive age, characterized by chronic anovulation, infertility, hyperandrogenemia and frequently, insulin resistance resulting in an increased prevalence of obesity, CVD and T2DM, reason why PCOS is consider a phenotype closely related to metabolic syndrome. Maher y cols. [9] have recently reported a germline missense mutation in the FEM1A gene in a PCOS woman that was absent in 198 control chromosomes; the authors propose FEM1A as a candidate gene for PCOS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
