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<or=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.
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 COPDpatients 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<or=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.
Authors: Rachel Damico; Tiffany Simms; Bo S Kim; Zenar Tekeste; Henry Amankwan; Mahendra Damarla; Paul M Hassoun Journal: Am J Respir Cell Mol Biol Date: 2010-05-06 Impact factor: 6.914
Authors: Jiyoun Yeo; Diego A Morales; Tian Chen; Erin L Crawford; Xiaolu Zhang; Thomas M Blomquist; Albert M Levin; Pierre P Massion; Douglas A Arenberg; David E Midthun; Peter J Mazzone; Steven D Nathan; Ronald J Wainz; Patrick Nana-Sinkam; Paige F S Willey; Taylor J Arend; Karanbir Padda; Shuhao Qiu; Alexei Federov; Dawn-Alita R Hernandez; Jeffrey R Hammersley; Youngsook Yoon; Fadi Safi; Sadik A Khuder; James C Willey Journal: BMC Pulm Med Date: 2018-03-05 Impact factor: 3.317