The influence of six cardiovascular polymorphisms on a first event of ischemic heart disease is modified by sex and age.
OBJECTIVE
To examine the contribution of six cardiovascular polymorphisms to the occurrence of a first event of ischemic heart disease (IHD) in a primary care population with a high prevalence of hypertension. Furthermore, we specified the data for sex and age.


METHODS
In this cross sectional case-control study, patients with a first event of IHD (157) and event-free controls (571) were studied. Both the groups were genotyped for the angiotensin II type 1 receptor (A1166C), angiotensinogen (M235 T), angiotensin converting enzyme (4656rpt), endothelial nitric oxide synthase (E298D), G-protein beta3 subunit (C825 T), and alpha-adducin (G460W) polymorphisms. Univariate and multivariate odds ratios (ORs) were calculated to assess the association between a first ischemic event and these polymorphisms. Sliding mean analyses were performed to show age-specific associations.


RESULTS
Multivariate ORs indicated a protective association for the carrier status of the T-allele of AGT, overall [OR = 0.69 (0.34-0.90)] and for males [OR = 0.58 (0.27-0.89)]. Sliding mean analyses showed a continuous protective association with IHD of the T-allele of AGT with increasing age in males, whereas in females an increased risk for IHD was observed with a maximum OR of 1.6 at the age of 56 years.


CONCLUSIONS
In this population the T-allele of the AGT polymorphism is protective for a first event of IHD in males.
Department of General Practice, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center, Maastricht, The Netherlands.
Arian W
AW
Plat
Henri E
HE
Stoffers
Peter W
PW
de Leeuw
Constant P
CP
van Schayck
Frank L
FL
Soomers
Arnold D
AD
Kester
Karin
K
Aretz
Abraham A
AA
Kroon
D000367:Age Factors; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics* / Q000517:prevention & control; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011320:Primary Health Care; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D000099291:Adducins
D000808:Angiotensinogen; 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; C544065:AGTR1 protein, human; C454420:G-protein beta3 subunit; C496314:NOS3 protein, human