COX-2 gene promoter polymorphism and coronary artery disease in middle-aged men: the Helsinki sudden death study.

Department of Medical Biochemistry, Medical School, University of Tampere, 33104 Tampere, Finland.
Mediators of Inflammation (Impact Factor: 2.42). 02/2008; 2008:289453. DOI: 10.1155/2008/289453
Source: PubMed

ABSTRACT Cyclooxygenase (COX) catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the -765G-->C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300) comprised of Finnish men who died suddenly. The area of atherosclerotic lesions in the coronary arteries was quantitated, and coronary narrowing was measured. The occurrence of myocardial infarction (MI) was assessed. Genotyping was by restriction endonuclease analysis. Men carrying the minor C allele had larger areas of complicated lesions (P = .024) and a higher number of coronary arteries that had over 50% stenosis (P = .036) compared to men representing the common GG genotype. The COX-2 polymorphism was not associated with MI. Our data suggest that COX-2 may be involved in plaque growth.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aspirin is the most commonly used antiplatelet drug for treatment of a serious vascular event, most notably stroke and myocardial infarction. However, despite the demonstrated benefit of aspirin, significant fraction of aspirin-treated patients may be resistant to the antiplatelet effects of the drug. The possible mechanisms of aspirin resistance (AR) are multifactorial. A genetic basis for AR has been suggested to exist. Therefore, the present study was taken up to investigate the role of -765G/C polymorphism (rs20417) in the cyclooxygenase-2 (COX-2) gene with AR in stroke patients. Four hundred and fifty stroke patients and four hundred and forty age and sex matched healthy controls were involved in the study. Baseline clinical data were collected and follow-up telephone interviews were conducted with patients at 3 months post event to determine stroke outcome using Modified Rankin Scale. Blood samples were collected and genotypes determined by polymerase chain reaction-restriction digestion technique. The association between the genotypes and outcome was evaluated by stepwise multiple logistic regression analysis. The COX-2 CC and GC genotype showed a significant association with bad outcome. Therefore, the carriers of C allele of COX-2 -765G/C polymorphism are more prone to AR in comparison with non-carriers. These results support a potential role of -765G/C COX-2 gene polymorphism with AR in ischemic stroke patients.
    Journal of Thrombosis and Thrombolysis 07/2012; · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The Cyclooxygenase-2 (COX-2) rs20417 polymorphism has been implicated in coronary artery disease (CAD) risk, but individually published studies have shown inconsistent results. The aim of this study was to clarify the effects of COX-2 rs20417 polymorphism on CAD risk. Methods A systematic literature search up to October 27, 2013 was carried out in PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases, and the references of retrieved articles were screened. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were analysed for co-dominant model (CC vs. GG), additive model (C vs. G), dominant model (CC + GC vs. GG), and recessive model (CC vs. GG + GC) to assess the association using fixed- or random-effect model. Results We identified nine articles (10 case-control studies) that included 3,439 cases and 14,182 controls for the present meta-analysis. Significant association between COX-2 rs20417 polymorphism and risk of CAD was observed in co-dominant model (OR = 0.64, 95% CI = 0.43-0.95, p = 0.026) and recessive model (OR = 0.77, 95% CI = 0.61-0.97, p = 0.025). Moreover, in the subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 0.28, 95% CI = 0.13–0.61, p = 0.001 for CC vs. GC + GG; OR = 0.24, 95% CI = 0.11–0.51, p < 0.001 for CC vs. GG) but not in Caucasians. Conclusions These results suggest that COX-2 rs20417 polymorphism may contribute to CAD development, especially in Asians.
    Heart Lung &amp Circulation 01/2014; · 1.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUD: The role of cyclooxygenase-2 (COX-2) single nucleotide polymorphisms has mostly been studied in relation to advanced atherosclerosis, but little is known how they contribute to preclinical disease. In the present study we analyzed whether COX-2 gene variants associate independently with the early subclinical markers of atherosclerosis, carotid intima-media thickness and carotid artery distensibility in a population of young healthy Caucasian adults. SNPs for association analysis were collected from the COX-2 gene and 5 kb up- and downstream of it. There were 19 SNPs available for analysis, four genotyped and fifteen imputed. Genotype data was available for 2442 individuals participating in the Cardiovascular Risk in Young Finns Study. Genotype imputation was performed using MACH 1.0 and HapMap II CEU (release 22) samples as reference. Association analysis was performed using linear regression with an additive model. PLINK was used for true genotyped SNPs and ProbABEL for imputed genotype dosages. False discovery rate was used to take into account multiple testing bias. Two of the COX-2 variants (rs689470, rs689462) associated with distensibility (p = 0.005) under the linear regression additive model. After adjustment with gender, age, body mass index and smoking status, association between these SNPs and distensibility remained significant (p = 0.031). Subjects carrying the minor alleles had higher value of carotid artery distensibility compared to the major allele homozygotes. However, after correcting p-values for multiple testing bias using false discovery rate, association was lost. Another COX-2 variant rs4648261 associated with mean carotid intima-media thickness (p = 0.046) and maximal carotid intima-media thickness (p = 0.048) in the linear regression model. Subjects carrying the minor allele of rs4648261 had lower values of mean and maximal carotid intima-media thickness compared to subjects homozygote for major allele. After adjustments the associations were lost with both mean and maximal carotid intima-media thickness. Thus, no statistically significant associations of the studied COX-2 variants with carotid artery distensibility or carotid intima-media thickness were found. Our results suggest that in a Finnish population, there are no significant associations between COX-2 variants and early atherosclerotic changes in young adulthood.
    BMC Medical Genetics 05/2012; 13:32. · 2.45 Impact Factor

Full-text (3 Sources)

Available from
May 27, 2014