Human Genetic Factors and Respiratory Syncytial Virus Disease Severity

Author:

Miyairi Isao1,DeVincenzo John P.1

Affiliation:

1. Department of Pediatrics, University of Tennessee Health Science Center, 50 N. Dunlap, Memphis, Tennessee 38103; Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave., Memphis, Tennessee 38163; and Children's Foundation Research Center, 50 N. Dunlap, Memphis, Tennessee 38103

Abstract

SUMMARY To explain the wide spectrum of disease severity caused by respiratory syncytial virus (RSV) and because of the limitations of animal models to fully parallel human RSV disease, study of genetic influences on human RSV disease severity has begun. Candidate gene approaches have demonstrated associations of severe RSV in healthy infants with genetic polymorphisms that may alter the innate ability of humans to control RSV (surfactants, Toll-like receptor 4, cell surface adhesion molecules, and others) and those that may control differences in proinflammatory responses or enhanced immunopathology (specific cytokines and their receptors). These studies are reviewed. They are valuable since an understanding of the direction of a polymorphism's effect can help construct a meaningful human RSV disease pathogenesis model. However, the direction, degree, and significance of the statistical association for any given gene are equivocal among studies, and the functional significance of specific polymorphisms is often not even known. Polymorphism frequency distribution differences associated with RSV infection arising from diversity in the genetic background of the population may be confounded further by multiple-hypothesis testing and publication bias, as well as the investigator's perceived importance of a particular pathogenic disease process. Such problems highlight the limitation of the candidate gene approach and the need for an unbiased large-scale genome-wide association study to evaluate this important disease.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Microbiology (medical),Public Health, Environmental and Occupational Health,General Immunology and Microbiology,Epidemiology

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