title: Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels.
abstract: BACKGROUND
  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 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.
  
  
  METHODS
  Anthropometric 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).
  
  
  RESULTS
  Genotype association analysis was significant for BMI (p < or = 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 < or = p < or = 0.006) and total cholesterol levels (0.001 < or = p < or = 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).
  
  
  CONCLUSIONS
  As 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.
authors.affiliation: Departamento de Genómica Estructural, Neocodex, Sevilla, Spain. mesaez@neocodex.es
authors.forename: María E
authors.initials: ME
authors.lastname: Sáez
authors.forename: María T
authors.initials: MT
authors.lastname: Martínez-Larrad
authors.forename: Reposo
authors.initials: R
authors.lastname: Ramírez-Lorca
authors.forename: José L
authors.initials: JL
authors.lastname: González-Sánchez
authors.forename: Carina
authors.initials: C
authors.lastname: Zabena
authors.forename: María J
authors.initials: MJ
authors.lastname: Martinez-Calatrava
authors.forename: Alejandro
authors.initials: A
authors.lastname: González
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Morón
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano-Ríos
mesh_terms: D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D002154:Calpain / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003971:Diastole; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci
chemical_list: D008076:Cholesterol, HDL; D005819:Genetic Markers; D002154:Calpain; C494426:Capn5 protein, human