Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study.
Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 and PTGS2. Using a case-cohort design, associations between genotype and CHD or stroke risk were evaluated using proportional hazards regression. In Caucasians, the reduced function PTGS1 -1006A variant allele was significantly more common among stroke cases compared to non-cases (18.2 versus 10.6%, P=0.027). In African Americans, the reduced function PTGS2 -765C variant allele was significantly more common in stroke cases (61.4 versus 49.4%, P=0.032). No significant relationships with CHD risk were observed. However, aspirin utilization appeared to modify the relationship between the PTGS2 G-765C polymorphism and CHD risk (interaction P=0.072). These findings suggest that genetic variation in PTGS1 and PTGS2 may be important risk factors for the development of cardiovascular disease events. Confirmation in independent populations is necessary.
Lee
C R
CR
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
North
K E
KE
Bray
M S
MS
Couper
D J
DJ
Heiss
G
G
Zeldin
D C
DC
D001741:Black or African American / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003327:Coronary Disease / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control / Q000652:urine; D051545:Cyclooxygenase 1 / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014481:United States; D044465:White People / Q000235:genetics
D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin