title: Genetic determinants of quantitative traits associated with cardiovascular disease risk.
abstract: Established risk factors for cardiovascular diseases (CVD) may be moderated by genetic variants. In 2403 unrelated individuals from general practice (mean age 40.5 years), we evaluated the influence of 15 variants in 12 candidate genes on quantitative traits (QT) associated with CVD (body mass index, abdominal obesity, glucose, serum lipids, and blood pressure). Prior to multiple testing correction, univariate analysis associated APOE rs429358, rs7412 and ATG16L1 rs2241880 variants with serum lipid levels, while LEPR rs1137100 and ATG16L1 rs2241880 variants were linked to obesity related QTs. After taking into account confounding factors and correcting for multiple comparisons only APOE rs429358 and rs7412 variants remained significantly associated with risk of dyslipidemia. APOE rs429358 variant almost tripled the risk in homozygous subjects (OR = 2.97; 95% CI 1.09-8.10, p < 0.03) and had a lesser but still highly significant association also in heterozygous individuals (OR = 1.67; 95% CI 1.24-2.10; p < 0.001). Associations with hypertension, diabetes mellitus, and metabolic syndrome were not significant after Bonferroni correction. The influence of genetic variation is more evident in dyslipidemia than in other analyzed QTs. These results may contribute to strategic research aimed at including genetic variation in the set of data required to identify subjects at high risk of CVD.
authors.affiliation: Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia. Electronic address: bozena.smolkova@savba.sk.
authors.forename: Božena
authors.initials: B
authors.lastname: Smolková
authors.affiliation: Clinical and Molecular Epidemiology, IRCCS San Raffaele, Pisana, 00166 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.affiliation: Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Verona
authors.initials: V
authors.lastname: Buociková
authors.affiliation: Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Mária
authors.initials: M
authors.lastname: Dušinská
authors.affiliation: Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Horská
authors.affiliation: National Transplant Organisation, 83303 Bratislava, Slovakia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kuba
authors.affiliation: National Transplant Organisation, 83303 Bratislava, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Džupinková
authors.affiliation: National Reference Center for Familial Hyperlipidemias, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Rašlová
authors.affiliation: Department of Virology, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Juraj
authors.initials: J
authors.lastname: Gašparovič
authors.affiliation: Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Slíž
authors.affiliation: Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ceppi
authors.affiliation: National Reference Center for Familial Hyperlipidemias, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Branislav
authors.initials: B
authors.lastname: Vohnout
authors.affiliation: Institute of Biophysics, Informatics and Biostatistics, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Ladislava
authors.initials: L
authors.lastname: Wsólová
authors.affiliation: Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Volkovová
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D000071183:Autophagy-Related Proteins; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D015897:Comorbidity; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D050171:Dyslipidemias / Q000453:epidemiology / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000235:genetics; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D054411:Receptors, Leptin / Q000235:genetics; D012306:Risk; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D018154:Slovakia / Q000453:epidemiology; D055105:Waist Circumference
chemical_list: C518959:ATG16L1 protein, human; D001057:Apolipoproteins E; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C515448:LEPR protein, human; D054411:Receptors, Leptin; D004247:DNA
keywords: Candidate gene; Cardiovascular disease; Genetic susceptibility; Quantitative trait; Risk factor