Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels.
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.
Sáez
María E
ME
Departamento de Genómica Estructural, Neocodex, Sevilla, Spain. mesaez@neocodex.es
Martínez-Larrad
María T
MT
Ramírez-Lorca
Reposo
R
González-Sánchez
José L
JL
Zabena
Carina
C
Martinez-Calatrava
María J
MJ
González
Alejandro
A
Morón
Francisco J
FJ
Ruiz
Agustín
A
Serrano-Ríos
Manuel
M
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
D008076:Cholesterol, HDL; D005819:Genetic Markers; D002154:Calpain; C494426:Capn5 protein, human