Functional rs20417 SNP (–765G>C) of Cyclooxygenase-2 Gene Does Not Predict the Risk of Recurrence of Ischemic Events in Coronary Patients: Results of a 7-Year Prospective Study

Abstract

Objectives: The –765G>C variation (rs20417 SNP) in the promoter of cyclooxygenase-2 (COX-2) gene has been demonstrated to lower COX-2 enzyme activity in the vasculature, thus affecting atherosclerotic plaque growth and stability. Therefore, this genetic variant may be a candidate influencing the residual risk. Methods: In 285 coronary patients the incidence of major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular deaths, non-fatal myocardial infarction and stroke, unstable angina and revascularization procedures, was monitored for a median of 7.8 years. The genotypes were obtained in 231 patients (81%) by PCR amplification and FAU I digestion. Results: 89 MACEs (38.5%) were recorded during the follow-up in genotyped patients. Their incidence was not different in patients with GC or CC when compared with those with GG genotype (46.2 vs. 35.5% respectively; p = 0.14). Kaplan-Meyer analysis did not demonstrate any influence of COX-2 genotypes on the event-free survival time (log-rank p = 0.55). After controlling for confounders, the –765G>C carrier status was not associated with significant variation in the risk of MACE or its individual components. Conclusions: These results suggest that the functional G–765C variant in the COX-2 gene is not a significant predictor of the recurrence of ischemic events in coronary patients.

The Link between Prostanoids and Cardiovascular Diseases

“…Similarly, the Helsinki Sudden Death Study has found that individuals carrying the CC genotype have larger atherosclerotic and complicated lesions in their coronary arteries than individuals with the GG genotype [ 69 ]. Finally, two studies did not find any association between rs20417 and CVDs [ 70 , 71 ]. Therefore, these differences may be due to the small sample size of some of these studies or might indicate a different impact of geographical ancestry on this variant.…”

Use of genetic data to guide therapy in arterial disease

“…A genetic polymorphism (rs20417) (COX-2) has been associated with lower COX-2 activity in the atherosclerotic plaque and a decreased risk of MI and stroke [14]. However, early COX-2 genetic studies had small sample sizes, and only some [15][16][17][18] but not all [19][20][21][22][23] have replicated these findings. Furthermore, an interaction between aspirin use and carriage of the COX-2 polymorphism has been reported.…”

PharmGKB summary

“…The C variant was initially found to be protective against myocardial infarction and stroke in a European Caucasian population [61], but this was not replicated [62]. Other studies have found that the C variant is associated with increased risk of stroke in African Americans but not White individuals [30,31].…”

“…Diabetics homozygous for the C allele of rs20417 had increased carotid-calcified plaque [63]. Other studies have shown no impact on secondary cardiovascular events [62] and aortic aneurysm [64]. The CC genotype was associated with asthma in Polish women [40].…”