Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis

Pasanen, Anu; Karjalainen, Minna K.; Bont, Louis; Piippo-Savolainen, Eija; Ruotsalainen, Marja; Goksör, Emma; Kumawat, Kuldeep; Hodemaekers, Hennie M.; Nuolivirta, Kirsi; Jartti, Tuomas; Wennergren, Göran; Hallman, Mikko; Rämet, Mika; Korppi, Matti

doi:10.1038/srep41653

Cited by 31 publications

(36 citation statements)

References 46 publications

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“…2 By the age of 2 years, nearly all children have been infected with RSV at least once, yet only 1-3% develop a severe disease requiring hospitalization, 2,3 suggesting a genetic predisposition to develop a severe disease. [4][5][6][7][8][9] In agreement with this possibility, a twin cohort study revealed a higher concordance in the hospitalization rates of identical twins when compared to fraternal twins, estimating that approximately 20% of the propensity to develop severe bronchiolitis upon RSV infection was attributable to genetic differences. 10 The potential relevance of genetic background to the degree of severity of bronchiolitis is further reinforced by the differences in the rate of RSV hospitalization observed in populations from different racial and ethnic backgrounds living in the same geographic region or country.…”

Section: Introductionmentioning

confidence: 74%

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients

et al. 2019

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BACKGROUND: Single-nucleotide polymorphisms (SNPs) that impact on the differential expression of interleukin 28B (IL28B) are implicated in the progression of viral-induced diseases. In this prospective longitudinal cohort study, we evaluated the association between IL28B SNPs rs12979860 and rs8099917 and the clinical outcome of bronchiolitis in pediatric patients. METHODS: A total of 682 infants suffering from bronchiolitis, categorized based on the final clinical outcome as mild or severe, were genotyped for IL28B SNPs rs12979860 and rs8099917. RESULTS: When infants were categorized exclusively based on the final clinical outcome, no association was established between IL28B SNPs and the severity of bronchiolitis. However, when stratified by sex, the homozygotes for the minor alleles of rs12979860 (T) and rs8099917 (G) were associated with a mild disease in girls but not in boys. CONCLUSION: SNPs rs12979860 and rs8099917 correlate with the severity of bronchiolitis and display a sex bias, where GG rs8099917 and TT rs12979860 genotypes are associated with a mild disease in girls but not in boys. These findings suggest that innate immunity and female sex links with the outcome of the diseases induced by respiratory viruses, such as RSV.

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Section: Introductionmentioning

confidence: 74%

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients

et al. 2019

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“…23 At present, genome-wide association studies (GWAS), including replication of identified loci, are the preferred method for gene discovery, but only one, relatively small, GWAS of bronchiolitis have been performed without genome-wide significant findings. 24 A number of susceptibility genes have been suggested from candidate gene studies.…”

Section: G R a P H I C A L Abstractmentioning

confidence: 99%

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Jartti

Smits

Bønnelykke

et al. 2018

Allergy

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Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.

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“…Genetic discoveries in GWAS require a very large number of participants, and large well-powered GWAS of respiratory viral infections per se have not yet been performed. One smaller GWAS of bronchiolitis was performed without genome-wide significant findings [34]. Candidate gene studies, most focusing on RSV bronchiolitis, have suggested several susceptibility genes related to immune regulation and surfactant proteins [35].…”

Section: Genetics and Epigenetics Of Asthma And Virus Susceptibilitymentioning

confidence: 99%

Role of viruses in asthma

et al. 2020

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Respiratory viral infections are the most important triggers of asthma exacerbations. Rhinovirus (RV), the common cold virus, is clearly the most prevalent pathogen constantly circulating in the community. This virus also stands out from other viral factors due to its large diversity (about 170 genotypes), very effective replication, a tendency to create Th2-biased inflammatory environment and association with specific risk genes in people predisposed to asthma development (CDHR3). Decreased interferon responses, disrupted airway epithelial barrier, environmental exposures (including biased airway microbiome), and nutritional deficiencies (low in vitamin D and fish oil) increase risk to RV and other virus infections. It is intensively debated whether viral illnesses actually cause asthma. Respiratory syncytial virus (RSV) is the leading causative agent of bronchiolitis, whereas RV starts to dominate after 1 year of age. Breathing difficulty induced by either of these viruses is associated with later asthma, but the risk is higher for those who suffer from severe RV-induced wheezing. The asthma development associated with these viruses has unique mechanisms, but in general, RV is a risk factor for later atopic asthma, whereas RSV is more likely associated with later non-atopic asthma. Treatments that inhibit inflammation (corticosteroids, omalizumab) effectively decrease RV-induced wheezing and asthma exacerbations. The anti-RSV monoclonal antibody, palivizumab, decreases the risk of severe RSV illness and subsequent recurrent wheeze. A better understanding of personal and environmental risk factors and inflammatory mechanisms leading to asthma is crucial in developing new strategies for the prevention and treatment of asthma.

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Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis

Cited by 31 publications

References 46 publications

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Role of viruses in asthma

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