Факторы риска формирования хронического полипозного риносинусита у детей с муковисцидозом

Abstract

The investigation of the pathogenesis of chronic rhinosinusitis in patients with cystic fibrosis (CF) and analysis of molecular biomarkers can promote the development of tailored approaches to its treatment and prevention. Objective. To analyze associations between sinonasal polyposis and genetic polymorphisms of the xenobiotic metabolizing enzymes (XMEs) in CF patients. Patients and methods. We performed a retrospective comparative analysis of 145 CF patients from the Russian Federation (RF) and 82 patients from the Republic of Belarus (RB). Patients provided blood samples that were later used for DNA extraction; clinical information was collected for all study participants. The diagnosis was based on the guidelines of the European and Russian Consensus. This was a case-control study. The XME gene polymorphisms were assessed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) or amplified fragment length polymorphism (AFLP) analysis with special primers. The following genes and polymorphic variants were chosen for the study: phase I (CYP2C9*3 (rs1057910; c.1075A>C; I359L), CYP2C9*2 (rs1799853; c.430C>T; R144C), CYP2C19*2 (rs4244285; c.681G>A), CYP2C19*3 (rs4986893; c.636G>A; W212X), CYP2D6*4 (rs3892097; c.1846G>A), CYP3A4*3 (rs4986910; M445T; c.1334T>C), CYP3A4*1B (rs2740574; c.-392C>T); phase II (deletions in GSTT1 and GSTM1; GSTP1 (c.313A>G); GCLC (TNR(GAG), c.-129C>T); GCLM (c.-588C>T); NAT2 (c.191G>A, c.282C>T, c.341T>C, c.434A>C, c.481C>T, c.590G>A, c.803A>G, c.845A>C, c.857G>A)). Results. Mean patient age was 12.69 ± 6.9 years (5.03–40.36) and did not vary between the RF and RB patients. The male to female ratio was 0.52:0.48 (118:109). Nasal polyposis was diagnosed in 61 patients (26.9%), while 166 children (73.1%) had no nasal polyps. We found that patients with chronic rhinosinusitis and nasal polyps were more likely to have ‘severe’ CFTR genotypes: 95.6% vs 4.4% of patients with a ‘mild’ genotype (р = 0.05). We observed no significant associations between nasal polyposis and analyzed XME gene polymorphisms, as well as glutathione metabolic genes. Conclusion. We found no associations between nasal polyposis and XME gene polymorphisms (phase 1 and 2), which suggests the need for further research aimed to identify other molecular mechanisms underlying the development of nasal polyps in CF patients. Key words: sinonasal polyposis, chronic rhinosinusitis, xenobiotic biotransformation enzymes, cystic fibrosis, glutathione, inflammation