Association of the −14C/GMETand the −765G/CCOX-2Gene Polymorphisms with the Risk of Chronic Rhinosinusitis with Nasal Polyps in a Polish Population

Abstract

Chronic rhinosinusitis with nasal polyps is strongly associated with other diseases, including asthma and allergy. The following study tested the association of the -765G/C polymorphism of cyclooxygenase-2 (COX-2) encoding gene and the -14C/G polymorphism of protooncogen MET (MET) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety-five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex-, age-, and ethnicity-matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients, 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls, and gene polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Ten percent of the samples have been confirmed by a second method single-strand conformation polymorphism (SSCP)-PCR. We reported that the -765G/C COX-2 (odds ratio [OR] 7.79; 95% confidence interval [CI] 4.88-12.4, p < 0.001) and the -14C/G MET (OR 2.83; 95% CI 1.74-4.61, p < 0.001) were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the -765C/G (OR 7.25; 95% CI 4.38-12.1, p < 0.001 and OR 7.61; 95% CI 4.47-12.6, p < 0.001) genotype of the COX-2 as wells as the -14C/G (OR 2.47; 95% CI 1.46-4.17, p < 0.001 and OR 2.59; 95% CI 1.54-4.37, p < 0.001) genotype of MET with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the -765G/C (OR 5.64;.03, p < 0.001, respectively) genotype of the COX-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that COX-2 and MET gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyp formation, which may also depend on asthma or allergy. Our results showed that the -765G/C polymorphism of COX-2 gene and the -14C/G polymorphism of the MET gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.

Genetics of chronic rhinosinusitis: State of the field and directions forward

“…A recent study in a Polish population also supports an association between MET and CRSwNP (-14C > G: OR, 2.83; 95% CI, 1.74-4.61; P < .001). 102 Additionally, these investigators have reported an association between CRSwNP and genetic variation in the lactoferrin gene, an antimicrobial peptide. 103 Confirmatory studies are needed.…”

“…101 Another recent publication reported an association between the gene encoding cyclooxygenase-2 ( PTGS2 ) and CRSwNP (-765G/C: OR, 6.05; 95% CI, 4.15-8.83; P < .001) among 195 CRSwNP patients and 200 matched controls. 102 …”

Evaluation of autoinflammatory disease genes in nasal polyposis*

“…Mesenchymal-epithelial transition factor (MET) is a transmembrane tyrosine kinase receptor and a protooncogene. A recent study showed that the -765G/C polymorphism of COX-2 gene and the -14C/G polymorphism of MET gene may result in an increased risk of developing nasal polyps in chronic rhinosinusitis (12).…”

IRAP-PCR As A Tool For Screening HERV Polymorphisms In Nasal Mucosal Swabs

“…[9] Similarly, correlations between gene polymorphisms and nasal polyposis have also been investigated by a number of different groups. [5] Findings imply that polymorphisms in several genes including MMP-9 [10] , LTC4S, NOS2A, PTGDR [11] , MET, COX-2 [12] , OSF-2 and LF [13] may also be associated with increased risk of developing nasal polyps. [5] However, these studies show limited ability in the detection of true genetic markers due to the heterogeneity of the mixed populations and/or concentration on populations from a small geographical region.…”

“…[5,[10][11][12][13][14] Given the high prevalence and morbidity associated with NP, more research is required to better understand its' aetiology and develop novel therapeutic strategies. [5,6,[10][11][12][13][14][15] Previously, the association between NP and infections of DNA viruses such as Epstein-Barr virus and human herpes virus-6 infection was studied. [16,17] However, a possible link between Human Endogenous Retrovirus (HERV) and NP has not been investigated yet.…”