Common variation in cytochrome P450 epoxygenase genes and... : Pharmacogenetics and Genomics (original) (raw)

ORIGINAL ARTICLES

Common variation in cytochrome P450 epoxygenase genes and the risk of incident nonfatal myocardial infarction and ischemic stroke

Marciante, Kristin D.a b; Totah, Rheem A.c; Heckbert, Susan R.a d g; Smith, Nicholas L.a d h; Lemaitre, Rozenn N.a b; Lumley, Thomasa e; Rice, Kenneth M.a e; Hindorff, Lucia A.a d; Bis, Joshua C.a b; Hartman, Brittanya; Psaty, Bruce M.a b d f g

aCardiovascular Health Research Unit

Departments of bMedicine

cMedicinal Chemistry

dEpidemiology

eBiostatistics

fHealth Services, University of Washington

gCenter for Health Studies, Group Health

hSeattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, Washington, USA

Correspondence to Kristin D. Marciante, MPH, PhD, Cardiovascular Health Research Unit, 1730 Minor Avenue Suite 1360, Seattle, WA 98101, USA

Tel: +1 253 318 1881; fax: +1 206 287 2662;

e-mail: [email protected]

Received 28 August 2007 Accepted 15 February 2008

Abstract

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.

Conclusion

Common variation in CYP2J2 is associated with the risk of myocardial infarction.