title: The contribution of six polymorphisms to cardiovascular risk in a Dutch high-risk primary care population: the HIPPOCRATES project.
abstract: This study was designed to examine the contribution of six polymorphisms to the occurrence of cardiovascular disease (CVD) in a Dutch primary care population with a high prevalence of cardiovascular risk factors. In this cross-sectional case-control study, 232 patients with CVD and 571 event-free controls were studied. Patients were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656rpt), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Univariate and multivariate odds ratios (ORs) were calculated to assess the relationship between genotypes and CVD. Receiver operating characteristic (ROC) analysis was used to quantify the contribution of the polymorphisms to the prediction of CVD. No differences in either genotype or allele frequencies were found between CVD cases and controls. Multivariate analyses, corrected for multiple testing according to Bonferroni, showed significant protective associations for the T-allele of AGT (OR=0.55 (0.34-0.84)) and for the T-allele of ADD1 (OR=0.52 (0.31-0.82)). ROC analysis showed only a very small improvement of CVD risk prediction by adding the six polymorphisms to a model with traditional risk factors. Our data suggest that a major attribution of the six polymorphisms to the cardiovascular risk prediction in a primary care population such as HIPPOCRATES is unlikely.
authors.affiliation: Department of General Practice, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: Plat
authors.forename: H E J H
authors.initials: HE
authors.lastname: Stoffers
authors.forename: O H
authors.initials: OH
authors.lastname: Klungel
authors.forename: C P
authors.initials: CP
authors.lastname: van Schayck
authors.forename: P W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: F L
authors.initials: FL
authors.lastname: Soomers
authors.forename: P M
authors.initials: PM
authors.lastname: Schiffers
authors.forename: A D M
authors.initials: AD
authors.lastname: Kester
authors.forename: A A
authors.initials: AA
authors.lastname: Kroon
mesh_terms: D000368:Aged; D000809:Angiotensins / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011320:Primary Health Care / Q000706:statistics & numerical data; D012372:ROC Curve; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D000099291:Adducins
chemical_list: D000809:Angiotensins; D002148:Calmodulin-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; D044140:Receptor, Angiotensin, Type 1; D000099291:Adducins; C454420:G-protein beta3 subunit; C496314:NOS3 protein, human