Cyclooxygenase-2 Polymorphism

Abstract

Prostaglandin endoperoxide H synthase (PGHS) catalyzes the conversion of arachidonic acid to PGH 2 , the first committed step in the biosynthesis of a range of lipid mediators, termed prostaglandins (PGs) and thromboxanes. 1 PGHS has both cyclooxygenase (COX) and hydroperoxidase activities. 2 Aspirin and a variety of nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the COX activity of PGHS 3 (Figure 1).

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

“…Numerous COX-1 and COX-2 single nucleotide polymorphisms (SNPs) have been identified, and a more complete discussion of them has been done by Ulrich et al (2002) and Cipollone and Patrono (2002). Silent and nonsilent SNPs have been identified in COX coding regions, and SNPs of unknown function have also been identified in COX introns, untranslated regions, and upstream regulatory regions (Fritsche et al, 2001;Cipollone and Patrono, 2002;Ulrich et al, 2002;Halushka et al, 2003;Konheim and Wolford, 2003).…”

Hypoxia, NSAIDs, and autism: A biocultural analysis of stressors in gametogenesis

“…Arachidonic acid is released by damaged tissue and then metabolized by COX (cyclooxygenase) enzyme (identified by Vane in 1971, Zarghi & Arfaei, 2011) to produce prostaglandins, including prostaglandin E2 (PGE2), which blocks the release of potassium from nociceptors and increases their sensitivity, amplifying feelings of inflammatory pain (Dafny, 2020; Dawidowicz et al, 2020). Complexity must be noted, however, since COX is only one of “at least 10 different proteins” contributing to the “biosynthesis and cellular actions” of PGE2 (Cipollone & Patrono, 2002). NSAIDs inhibit the work of the COX enzyme by “competing with arachidonic acid for the active site of the enzyme” (Dawidowicz et al, 2020) and in so doing, prevent the synthesis of prostaglandins and cancel out the action of pain signaling (though other molecules, such as histamine, lactic acid, and serotonin may also sensitize or excite nociceptors) (Dafny, 2020).…”

“…Typically, the cells in adult bodies express little or no COX‐2 enzyme, and prostaglandins (as well as prostacyclin and thromboxane A2) are not synthesized (Dawidowicz et al, 2020). A range of stressors (both natural and unexpected), however, can induce COX‐2 expression in endothelial cells, including hormones, proinflammatory cytokines, endotoxin, lipopolysaccharides, growth factors, mitogens, oncogenes and tumor promoters, and even “shear stress” (Cambria‐Kiely & Gandhi, 2002; Cipollone & Patrono, 2002; Zarghi & Arfaei, 2011). In the lungs, for example, the stressor of cigarette smoke triggers epithelial cells lining the bronchus to respond with pro‐inflammatory cytokines and the up‐regulation of inflammation‐related proteins, including COX‐2 (Moraes et al, 2017).…”

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

“…The G>C substitution at position –765 in the COX-2 proximal promoter (–G765C, dbSNP rs20417) has been associated with lower COX-2 gene transcription and enzyme activity [11]. This effect has been attributed to the fact that this sequence variation alters the binding of the transcription factor Sp1 to this region [12]. Consistently, the COX-2 –765C variant has been associated with a significant reduction in plasma C-reactive protein [11,13,14], a sensitive marker of low-grade inflammation, as well as with a reduced expression of matrix metalloproteinases in atherosclerotic plaques [15].…”