Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: A systematic review and meta-analysis

McNally, James Dayre; Sampson, Margaret; Matheson, Loren A.; Hutton, Brian; Little, Julian

doi:10.1002/ppul.22877

Cited by 59 publications

(56 citation statements)

References 69 publications

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“…Polymorphisms in SFTPA2 (G223L) and SFTPD (M11T) were shown to be associated with severity of RSV infection in cohorts of patients from Finland and the United States (83, 92, 153). Several studies have also demonstrated a significant association between the FokI start codon polymorphism of the vitamin D receptor gene (VDR) (which codes for an intracellular receptor and transcription factor) and severity of RSV bronchiolitis (68, 80, 102). The FokI polymorphism exacerbates RSV pathogenesis by coding for a VDR that fails to restrain STAT1-mediated antiviral cytokine responses, leading to increased immunopathology (141).…”

Section: Respiratory Syncytial Virusmentioning

confidence: 99%

Human Genetic Determinants of Viral Diseases

et al. 2017

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Much progress has been made in the identification of specific human gene variants that contribute to enhanced susceptibility or resistance to viral diseases. Herein we review multiple discoveries made with genome-wide or candidate gene approaches that have revealed significant insights into virus–host interactions. Genetic factors that have been identified include genes encoding virus receptors, receptor-modifying enzymes, and a wide variety of innate and adaptive immunity-related proteins. We discuss a range of pathogenic viruses, including influenza virus, respiratory syncytial virus, human immunodeficiency virus, human T cell leukemia virus, human papilloma virus, hepatitis B and C viruses, herpes simplex virus, norovirus, rotavirus, parvovirus, and Epstein-Barr virus. Understanding the genetic underpinnings that affect infectious disease outcomes should allow tailored treatment and prevention approaches in the future.

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Section: Respiratory Syncytial Virusmentioning

confidence: 99%

Human Genetic Determinants of Viral Diseases

et al. 2017

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“…There is also evidence linking vitamin D insufficiency and deficiency to an increased incidence of acute bronchiolitis. A recent systematic review and meta‐analysis concluded that polymorphisms at the VDR level—which might be linked to functional vitamin D deficiency—are usually present in patients hospitalized because of severe RSV bronchiolitis, which is strongly associated with the development of wheezing and asthma later on in life …”

Section: Vitamin D Deficiency and Viral‐induced Exacerbations Of Asthmamentioning

confidence: 99%

Vitamin D modulation of innate immune responses to respiratory viral infections

et al. 2016

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Vitamin D, in addition to its classical functions in bone homeostasis, has a modulatory and regulatory role in multiple processes, including host defense, inflammation, immunity, and epithelial repair. Patients with respiratory disease are frequently deficient in vitamin D, implying that supplementation might provide significant benefit to these patients. Respiratory viral infections are common and are the main trigger of acute exacerbations and hospitalization in children and adults with asthma and other airways diseases. Respiratory monocytes/macrophages and epithelial cells constitutively express the vitamin D receptor. Vitamin D, acting through this receptor, may be important in protection against respiratory infections. Whether the in vitro findings can be translated into a substantial in vivo benefit still remains uncertain. Here we review the in vitro data on the role of vitamin D in antiviral innate immunity, the data concerning the deficient levels of vitamin D in lung diseases, and the in vivo role of supplementation as protection against respiratory viral infections in healthy individuals and in patients with chronic respiratory diseases. Finally, we suggest ways of improving the effectiveness of vitamin D as an adjuvant in the prevention and treatment of acute respiratory infections.

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“…Genetic factors may also explain the conflicting results on the efficacy of vitamin D (VD), the fat‐soluble‐secosteroid able to potentiate the secretion of type 1 interferon, of chemokines (CXCL8 and CXCL10) and cytokines (TNF‐α and IL‐6) from human BECs, in response to RSV infection . Indeed, in children from South Africa, the Thr1Meth, but not the JUN (c.750G/A) SNP allele of the VD receptor, was identified as a risk factor for severe RSV disease and genotype analysis performed in different populations showed positive relationships between VD receptor FokI (rs2228570) SNP and RSV disease severity . Surfactant protein (SP)‐A and Surfactant protein‐D gene polymorphisms have also been proposed to explain host susceptibility to respiratory disease .…”

Section: Viral and Host Factors That May Downregulate The Innate Antimentioning

confidence: 99%

Respiratory syncytial virus–Host interaction in the pathogenesis of bronchiolitis and its impact on respiratory morbidity in later life

Rossi

Colin

2017

Pediatric Allergy Immunology

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Respiratory syncytial virus (RSV) is the most common agent of severe airway disease in infants and young children. Large epidemiologic studies have demonstrated a clear relationship between RSV infection and subsequent recurrent wheezing and asthma into childhood, thought to be predominantly related to long-term changes in neuroimmune control of airway tone rather than to allergic sensitization. These changes appear to be governed by the severity of the first RSV infection in infancy which in term depends on viral characteristics and load, but perhaps as importantly, on the genetic susceptibility and on the constitutional characteristic of the host. A variety of viral and host factors and their interplay modify the efficiency of the response to infection, including viral replication and the magnitude of structural and functional damage to the respiratory structures, and ultimately the extent, severity, and duration of subsequent wheezing.

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Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: A systematic review and meta-analysis

Abstract: Available literature supports an association between the FokI polymorphism and severe RSV disease. Determination of VDR receptor polymorphism status could help predict high-risk infants who might benefit from preventive measures.

Cited by 59 publications

References 69 publications

Human Genetic Determinants of Viral Diseases

Human Genetic Determinants of Viral Diseases

Vitamin D modulation of innate immune responses to respiratory viral infections

Respiratory syncytial virus–Host interaction in the pathogenesis of bronchiolitis and its impact on respiratory morbidity in later life

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