Chronic Rhinosinusitis with Nasal Polyps - Symptoms, Heredity and Genetics

Sammanfattning: ABSTRACT Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by long-term inflammation of the paranasal sinuses combined with bilateral glassy protuberances from the middle meatus of the nasal cavity. This disease has an unknown cause, affects roughly 3% of the population and causes symptoms from the upper airways. This thesis addresses the heredity, symptoms and possible genetic factors of chronic rhinosinusitis with nasal polyps. METHODS/RESULTS: Paper I investigates the prevalence of nasal polyps in a group of 410 first-degree relatives to patients with the same condition using nasal endoscopy and compares them to a control group of 1387 individuals from a previous study. 13.4% of the relatives had nasal polyps themselves, compared to 2.7% from the control group. The relative risk of the first-degree relatives having nasal polyps when compared to the control group was 4.9. Paper II studies the symptoms and risk factors of 367 patients with CRSwNP and compares them to 1349 polyp-free controls. Symptoms and risk factors were gathered by a structured interview and compared in a multiple logistic regression model. Higher age, male sex, nasal blockage, impaired sense of smell, nasal secretions and asthma was more common among subjects with CRSwNP whereas smoking was less frequent. Paper III is a family-based genome-wide association study that compares single nucleotide polymorphisms between 406 participants with CRSwNP and 376 of their polyp-free first-degree relatives. After association testing and post-GWAS analysis; HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 were the most significant. Of these five genes, only HLA-DRA has been implicated in CRSwNP previously. Paper IV measures the expression levels of ten of the most significant genes from Paper III in peripheral blood from 76 individuals with CRSwNP and 45 of their polyp-free relatives and studies their eQTL patterns. NDUFS5, CPEB3, HLCS and BICD2 were upregulated in cases. HLCS, LYZ, PDGFD and TIAM1 showed differences in expression when examining participants with different genotypes. CONCLUSIONS: First-degree relatives of patients with CRSwNP have an almost fivefold increased relative risk of having nasal polyps themselves when compared to controls. Nasal secretion, nasal blockage and decreased sense of smell are more common among subjects with CRSwNP than among controls. HLCS, BICD2, VSIR and SLC5A1 are potential new genes of interest in CRSwNP. HLA-DRA is strengthened as a research target. NDUFS5, CPEB3, HLCS and BICD2 are upregulated in peripheral blood samples from patients with CRSwNP when compared to controls. HLCS, LYZ, PDGFD and TIAM1 displayed differences when comparing allelic expression.