Case-control study of (CCTTT)n polymor-phism of NOS2A in nasal polyposis

Resumen

Background:The etiopathogenesis of nasalpolyps is largely unknown. Some geneticstudies have being performed, mostlyfocused in hereditary observations or thecorrelation with certain leukocyte antigen(HLA) alleles. Nitric Oxide, an importantsignaling molecule implicated in the patho-physiology of several airway diseases, isproduced by the inducible NO synthaseenzyme NOS2A and is generated at highlevels in certain types of inflammation, par-ticularly in paranasal sinuses. A VariableNumber Tandem Repeats (VNTR), con-sisting in a pentanucleotide polypyrimidinemicrosatellite (CCTTT)n, is found in thepromoter region of the NOSA2 gene.The present study was designed to analyzethe (CCTTT)n polymorphism in patientswith nasal poliposis.Material and methods:We have evaluateda population of 245 unrelated Caucasianindividuals (106 patients and 136 controls).Patients were diagnosed of nasal poliposisfollowing EPO3S guidelines. Skin pricktests were performed in all individuals.From 106 patients with nasal poliposis 51had also asthma and from these last 25had also aspirin hypersensitivity. DNA wasextracted from peripheral blood using aDNA extraction kit and Polymerase ChainReaction (PCR) amplification of the corre-sponding fragments from the NOS2A pro-moter region was performed. Thepolymorphism was analyzed by an electro-phoretic method and by direct sequencing.TheSPSSsoftware and theSHEsis soft-ware platform were employed for statisticalanalyses. Different cut-offs related to thenumber of CCTTT repeats were analyzed.Results:A significant association wasdetected for 15-repeats (Fisher’s p 0.041)and 16-repeats (Fisher’s p 0.032) cutoffswith nasal polyposys. This association waseven higher in patients with associatedasthma (Fisher’s p values of 0.013 and0.009, respectively) and ASA triad (Fisher’sp values of 0.006 and 0.001, respectively). Conclusion:This result strongly suggeststhat the number of CCTTT repeats in thepromoter region of NOS2A could be asso-ciated with the inflammatory process ofnasal poliposis. This fact might be due toputative modifications at the transcriptionlevel of the NOSA2 gene.