Dataset Information

CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study.

ABSTRACT: OBJECTIVE:The cytochromes P450 epoxygenases CYP2J2 and CYP2C8 synthesize epoxyeicosatrienoic acids, which regulate endothelial function. We sought to determine if genetic variation in CYP2J2 and CYP2C8 was associated with coronary heart disease risk. METHODS:We genotyped 2065 Atherosclerosis Risk in Communities study participants (1085 incident coronary heart disease cases, 980 noncases) for polymorphisms in CYP2J2 and CYP2C8. Using a case-cohort design, associations between genotype and incident coronary heart disease risk were evaluated using proportional hazards regression. The influence of cigarette smoking on these associations was also evaluated. False discovery rate q-values were estimated to minimize the impact of the multiple statistical comparisons completed. All analyses were race stratified. RESULTS:The CYP2J2 G-50T polymorphism variant -50T allele was associated with significantly lower risk of incident coronary heart disease in African-Americans (adjusted hazard rate ratio 0.58, 95% confidence interval 0.35-0.96, P=0.036, q=0.051); however, no significant association was observed in Caucasians. Overall, the I264M, I269F, and K399R polymorphisms in CYP2C8 were not significantly associated with risk of incident coronary heart disease. In Caucasians, the relationship between the I264M and K399R polymorphisms and incident coronary heart disease risk was significantly modified by cigarette smoking status (P for interaction=0.008, q=0.064), with the highest risk observed in smokers carrying at least one variant allele. CONCLUSIONS:The G-50T polymorphism in CYP2J2 may be an important risk factor for the development of coronary heart disease events in African-Americans, whereas cigarette smoking may modify the relationship between the I264M and K399R polymorphisms in CYP2C8 and coronary heart disease risk in Caucasians. Confirmation of these findings in an independent population is warranted.

SUBMITTER: Lee CR

PROVIDER: S-EPMC1947003 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study.

Lee Craig R CR North Kari E KE Bray Molly S MS Couper David J DJ Heiss Gerardo G Zeldin Darryl C DC

Pharmacogenetics and genomics 20070501 5

<h4>Objective</h4>The cytochromes P450 epoxygenases CYP2J2 and CYP2C8 synthesize epoxyeicosatrienoic acids, which regulate endothelial function. We sought to determine if genetic variation in CYP2J2 and CYP2C8 was associated with coronary heart disease risk.<h4>Methods</h4>We genotyped 2065 Atherosclerosis Risk in Communities study participants (1085 incident coronary heart disease cases, 980 noncases) for polymorphisms in CYP2J2 and CYP2C8. Using a case-cohort design, associations between genot ...[more]

PMID: 17429317

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Project description:BACKGROUND:Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE:To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN:This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS:Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS:The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS:At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION:HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

Dataset Information

CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study.

Publications

CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study.

Similar Datasets

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