BACKGROUND: Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) are enzymes involved in prostaglandin and prostacyclin synthesis, which have been linked to cardiovascular disease risk. We hypothesized that genetic variations altering the function of these enzymes would modify the risk of myocardial infarction (MI). METHODS: In a Chinese case control study of MI patients (n=356) and healthy controls (n=350), we investigated the roles of polymorphisms in the PGIS gene (CYP8A1) and the COX-2 gene (PTGS2) using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The CC genotype of CYP8A1 and the -765CC genotype of PTGS2 were more common in the MI patients than in the control subjects (p=0.041, p=0.012, respectively). The odds ratio (OR) estimated by the combined analysis for the CYP8A1 CC and PTGS2-765CC genotypes [OR =5.44; 95% confidence interval (CI): 3.12-7.23] was markedly higher than that estimated separately for the CYP8A1 CC genotype (OR=1.37; 95% CI: 0.95-2.85) or the PTGS2 -765CC genotype (OR=2.92; 95% CI: 1.78-5.76) alone. CONCLUSIONS: The CC genotype of CYP8A1 or the -765CC genotype of PTGS2 is associated with MI, respectively. Furthermore, the significantly combined effects of these two gene variants in the arachidonic acid metabolic pathway indicate that combining the effects of a modest number of genes, whose products are known to act in a pathophysiological manner, could be a useful method to explore the association of genetic polymorphisms and polygenic inheritance disease.
BACKGROUND:Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) are enzymes involved in prostaglandin and prostacyclin synthesis, which have been linked to cardiovascular disease risk. We hypothesized that genetic variations altering the function of these enzymes would modify the risk of myocardial infarction (MI). METHODS: In a Chinese case control study of MI patients (n=356) and healthy controls (n=350), we investigated the roles of polymorphisms in the PGIS gene (CYP8A1) and the COX-2 gene (PTGS2) using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The CC genotype of CYP8A1 and the -765CC genotype of PTGS2 were more common in the MI patients than in the control subjects (p=0.041, p=0.012, respectively). The odds ratio (OR) estimated by the combined analysis for the CYP8A1 CC and PTGS2-765CC genotypes [OR =5.44; 95% confidence interval (CI): 3.12-7.23] was markedly higher than that estimated separately for the CYP8A1 CC genotype (OR=1.37; 95% CI: 0.95-2.85) or the PTGS2 -765CC genotype (OR=2.92; 95% CI: 1.78-5.76) alone. CONCLUSIONS: The CC genotype of CYP8A1 or the -765CC genotype of PTGS2 is associated with MI, respectively. Furthermore, the significantly combined effects of these two gene variants in the arachidonic acid metabolic pathway indicate that combining the effects of a modest number of genes, whose products are known to act in a pathophysiological manner, could be a useful method to explore the association of genetic polymorphisms and polygenic inheritance disease.
Authors: In Jai Kim; Sang Hoon Kim; Dong Hoon Cha; Sang Wook Lim; Jae Youn Moon; Jung Oh Kim; Chang Soo Ryu; Han Sung Park; Jung Hoon Sung; Nam Keun Kim Journal: Genes Genomics Date: 2019-06-05 Impact factor: 1.839