Impact of -1607 1G/2G MMP1 gene polymorphism on the morbidity and clinical course of chronic rhinosinusitis with nasal polyps.

UNLABELLED: Polyps within the nose and nasal sinuses are symptoms of both local conditions such as chronic bacterial or fungal rhinosinusitis, and systemic diseases such as cystic fibrosis, hypogammaglobulinemia, NSAID hypersensitivity syndrome, bronchial asthma as well as Kartagener's syndrome, Young's syndrome, Churg-Strauss' syndrome and Woakes' syndrome. The pathomechanism responsible for formation of nasal polyps remains a matter of dispute as well as the subject of numerous studies. Despite the proven role of metalloproteinases and their inhibitors in the pathomechanism of inflammation, the role of their respective polymorphisms has not been fully confirmed to date.

OBJECTIVES: 1. The assessment of genetic predisposition to chronic rhinosinusitis with nasal polyps on the basis of the analysis of 1G/2G polymorphism at position -1607 of the MMP1 gene; 2. Determination of correlation between the variability of MMP1 gene and the natural history of chronic rhinosinusitis with nasal polyps; 3. Determination of the relationship between epidemiological or clinical features and the results of genotyping of patients with chronic rhinosinusitis with nasal polyps Material and method The study included 206 patients subjected to surgical treatment due to chronic rhinosinusitis with nasal polyps and 463 healthy volunteers hospitalized at the Department of Otolaryngology and Oncological Laryngology of the Medical University of Łódź. The analysis of 1G/2G polymorphism at position -1607 of the MMP1 gene was based on TaqMan® SNP Genotyping Assays (Applied Biosystems, USA).

RESULTS: The 1G/2G polymorphic variants at position -1607 of the MMP1 gene did not predispose patients to CRSNP+, although a trend towards increased risk of the disease could be observed in the mutated allele (InsG) carriers. However, the correlation was not statistically significant (OR 1.175; 95%CI 0.5391-1.1142; p=0.16822). In comparison to wild-type homozygotic genotype, the carriers of -1607 1G/2G mutated allele (InsG) were characterized by: 1. significantly younger age at which surgical treatment was required following conservative treatment that had proven insufficient to control CRSNP+ (p=0.025); 2. significantly higher rate of recurrence requiring surgical intervention (p=0.002); 3. trend towards higher intensity of sinus-related symptoms as assessed using a VAS scale; 4. more frequent incidence of CRSNP+ with hypersensitivity to aspirin (correlation on the border of significance, p=0.054); 5. less common bronchial asthma comorbidity (p=0.021); 6. family history of CSRNP+ (p=0.045).

CONCLUSIONS: The 1G/2G polymorphism at position -1607 of the MMP1 gene may impact patients' predisposition to chronic rhinosinusitis with nasal polyps. Polymorphic variants are consistent with overall morbidity and may constitute risk variants. The status of a carrier of mutated (G insertion) allele with regard to the 1G/2G polymorphism at position -1607 within the MMP1 gene may determine a pathological phenotype associated with a more severe clinical course of CRSNP+ including earlier onset and disease recurrence.