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.


METHODS
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).


CONCLUSIONS
The prevalence of COX2 and p53 risk-alleles contributes towards susceptibility to the disease.
Arif
Ehtesham
E
Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India.
Vibhuti
Arpana
A
Deepak
Desh
D
Singh
Bhawani
B
Siddiqui
Mohd Saeed
MS
Pasha
M A Qadar
MA
D000483:Alleles; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005787:Gene Frequency; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human