| 1. |
- Bohman, Anton, et al.
(author)
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A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis.
- 2017
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Journal article (peer-reviewed)abstract
- The pathogenesis of chronic rhinosinusitis with nasal polyps is largely unknown. Previous studies have given valuable information about genetic variants associated with this disease but much is still unexplained. Our goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study.427 patients (293 males and 134 females) with CRSwNP and 393 controls (175 males and 218 females) were recruited from several Swedish hospitals. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX). Analyses of pathway enrichment, gene expression levels and expression quantitative trait loci were then performed in turn.None of the analysed SNPs reached genome wide significant association of 5.0 x 10-8. Pathway analyses using our top 1000 markers with the most significant association p-values resulted in 138 target genes. A comparison between our target genes and gene expression data from the NCBI Gene Expression Omnibus database showed significant overlap for 36 of these genes. Comparisons with data from expression quantitative trait loci showed the most skewed allelic distributions in cases with chronic rhinosinusitis with nasal polyps compared with controls for the genes HLCS, HLA-DRA, BICD2, VSIR and SLC5A1.Our study indicates that HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 could be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. HLA-DRA has been associated with chronic rhinosinusitis with nasal polyps in previous studies and HLCS, BICD2, VSIR and SLC5A1 may be new targets for future research.
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| 2. |
- Bohman, Anton
(author)
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Chronic Rhinosinusitis with Nasal Polyps - Symptoms, Heredity and Genetics
- 2019
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 3. |
- Bohman, Anton, et al.
(author)
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Heredity of nasal polyps.
- 2015
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In: Rhinology. - 0300-0729. ; 53:1, s. 25-8
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Journal article (peer-reviewed)abstract
- Nasal polyps is a common disease but little is known about its` pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps.
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| 4. |
- Bohman, Anton, et al.
(author)
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Heredity of nasal polyps
- 2015
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In: Rhinology. - 0300-0729 .- 1996-8604. ; 53:1, s. 25-28
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Journal article (peer-reviewed)abstract
- Background: Nasal polyps is a common disease but little is known about its' pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. Methodology: Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. Results: During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. Conclusion: This study strongly indicates that heredity is a factor of importance for development of nasal polyps.
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| 5. |
- Bohman, Anton, et al.
(author)
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Relative frequencies of symptoms and risk factors among patients with chronic rhinosinusitis with nasal polyps using a case-control study
- 2018
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In: Acta Oto-Laryngologica. - : TAYLOR & FRANCIS LTD. - 0001-6489 .- 1651-2251. ; 138:1, s. 46-49
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Journal article (peer-reviewed)abstract
- Objectives: The aim of this study was to investigate the relative frequency of important symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), the link between CRSwNP and the lower airways and the importance of smoking in CRSwNP.Method: Three hundred and sixty-eight patients with CRSwNP and 1349 controls were recruited to the study and underwent a structured interview about symptoms from the upper and lower airways, and about smoking habits. Furthermore, all participants were clinically examined using nasal endoscopy.Results: Due to interactions between the outcome variables, a multiple logistic regression model was fitted to the data. Nasal secretions, nasal blockage and impaired sense of smell were symptoms associated with CRSwNP. Furthermore, male gender, increasing age and asthma were also associated with the disease. Current smoking was less frequent among patients with CRSwNP.Conclusion: By comparing symptoms and risk factors of patients with CRSwNP with those of a large population-based control group and testing them in a multiple logistic regression model, we have been able to generate data that address key research interests in CRSwNP.
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| 6. |
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| 7. |
- Torinsson Naluai, Åsa, 1968, et al.
(author)
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Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.
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