COX2 and p53 risk-alleles coexist in COPD

Background: Cigarette smoke stimulates airway epithelial cells to release pro-inflammatory cytokines which influence various inflammation-related genes, including COX2, whereas p53 expression is known to alter in such a condition. Since both the genes share several common physiological functions including inflammation and oxidative stress, we investigated within gene and gene-gene interactions towards susceptibility to the disease. Method: In a prospective gene-association study we conducted PCR-RFLP for genotyping the COX2 -765G/C and 8473T/C and p53 72Pro/Arg polymorphisms in 229 COPD patients and 147 healthy controls. Results: The -765GC+CC genotypes of COX2 and Pro/Pro+Pro/Arg genotypes of p53 were prevalent in patients with significant odds ratio, 2.05 and 2.30, respectively (p=0.001; p=0.009, respectively), as a consequence, the -765C and 72Pro alleles were prevalent (p <= 0.001). Individually, the 8473T/C polymorphism did not associate with the disease (p=NS), however, it did in the haplotype -765C:8473C, which was significantly higher in patients (p<0.0001). Based on its prevalence, the three alleles were identified as risk-alleles in patients. The combinations of the genotypes containing 3, 4 and 5 risk alleles of the 3 polymorphisms were significantly over-represented in patients, whereas, the genotypes combinations containing 0, 1 and 2 risk alleles were significantly higher in controls (p=0.0004). The pairwise gene-gene interactions validated prevalence of risk-alleles associated pairing of genotypes such as the Pro/Pro+ Pro/Arg with -765GC+-765CC in patients (p=0.01). Conclusion: The prevalence of COX2 and p53 risk-alleles contributes towards susceptibility to the disease. (C) 2008 Elsevier B.V. All rights reserved.