Common variation in cytochrome P450 epoxygenase genes and the risk of incident nonfatal myocardial infarction and ischemic stroke.
OBJECTIVE
The biologically active epoxyeicosatrienoic acids have protective vascular effects. CYP2J2, CYP2C8, and CYP2C9 are known to be a source of epoxyeicosatrienoic acids in cardiac tissues. We conducted a population-based, case-control study at Group Health to determine whether common genetic variation in the CYP2J2, CYP2C8, and CYP2C9 genes was associated with the risk of myocardial infarction and ischemic stroke.


METHODS
We used publicly available single nucleotide polymorphism discovery data from a mixed race panel of 90 individuals to select 30 tag-single nucleotide polymorphisms that were genotyped in 856 myocardial infarction cases, 368 stroke cases and 2688 controls. We used logistic regression to estimate additive associations. To account for multiple testing, we report q values alongside findings with P<0.05.


RESULTS
Variation in CYP2J2 was associated with myocardial infarction risk (P=0.027, q=0.081). Two intronic CYP2J2 tag-single nucleotide polymorphisms, rs10889160 and rs11572325 were associated with an increased risk of myocardial infarction (odds ratio: 1.24, 95% confidence interval: 1.07-1.43, P=0.004, q=0.090, and odds ratio: 1.27, 95% confidence interval: 1.08-1.51, P=0.006, q=0.090, respectively). No evidence of an association was found between variation in CYP2J2 and stroke and there was no association between variation in CYP2C8 or CYP2C9 and myocardial infarction or stroke.


CONCLUSIONS
Common variation in CYP2J2 is associated with the risk of myocardial infarction.
Marciante
Kristin D
KD
Cardiovascular Health Research Unit, Seattle, Washington 98101, USA. marciant@u.washington.edu
Totah
Rheem A
RA
Heckbert
Susan R
SR
Smith
Nicholas L
NL
Lemaitre
Rozenn N
RN
Lumley
Thomas
T
Rice
Kenneth M
KM
Hindorff
Lucia A
LA
Bis
Joshua C
JC
Hartman
Brittany
B
Psaty
Bruce M
BM
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics*; D016017:Odds Ratio; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology* / Q000235:genetics*
C000717350:CYP2J2 protein, human; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D000090762:Cytochrome P-450 CYP2J2