TABLE 2.

Genetic associations with respiratory viral infectiona

Group and geneVirusEffect of studied SNPReference(s)
Inflammatory mediators
    CCL5SARS-CoV−28G allele, which increases NF-κB binding, increases the risk of fatality239
    IFN-αRSV−453T allele (no known function) association on limited genome-wide approach150
    IFN-γRSVIncreased IFN-γ production associated with increased disease severity108
SARS-CoV−874A allele, which reduces NF-κB binding and increases SARS susceptibility57
    IL-4RSV−589T allele, which increases transcription factor binding affinity, associated with increased risk56
RSV−589T allele study130
RSVStudy of 5q31 Th2 cytokine gene cluster102
RSVNo association with −589T SNP271
    IL-6RV/RSV−174C allele, which decreases IL-6 expression, associated with increased risk of OM11
RSVHigh-producing IL-6 alleles associated with shorter hospital stay108
    IL-8RSV−251A allele, which increases IL-8 expression, associated with increased risk of bronchiolitis136
−251A allele, which increases IL-8 expression, associated with increased risk of wheeze110
−781C/T allele, which alters promoter binding, associated with asthma but not RSV bronchiolitis273
    IL-9RSVNo association129
    IL-10RV/RSVHigh-producing IL-10 allele associated with increased risk of OM11
RSV−592C allele (no known function) associated with bronchiolitis129
IVNo effect on vaccine response324
    IL-13RSV−1112T allele, which increases binding affinity, associated with increased risk of severe RSV infection271
Study of 5q31 Th2 cytokine gene cluster102
Arg130Gln, which alters IL-13Rα1 binding, associated with increased risk of persistent wheeze92
    IL-18RSV133G/C allele, which may alter STAT binding and IL-18 expression, associated with increased RSV bronchiolitis270
SARS-CoV−607T allele (no known function) associated with increased nasal shedding54
    TGF-βRSV−509T allele, which increases TGF-β1 expression, associated with RSV wheeze131
    TNFRSVNo association108, 129, 267
SARS-CoV−204C/T allele (no known function) associated with protective effect345
    PGI2RSVNo association123
Receptors
    CCR5RSV−2459/G (decreases expression) and 2554/T alleles associated with severe RSV bronchiolitis135
    CD14RSV−550C/T allele, which increases levels of soluble CD14, associated with risk of severe RSV bronchiolitis143
No association269, 322
SARS-CoV−155C/C allele, which decreases level of soluble CD14, increases risk of SARS-CoV356
    CX3CR1RSVThr280Met (no known function) increases risk of RSV LRTI14
    E selectinRSVNo association178
    FCεR1ARSV−66C allele (no known function) association on limited genome-wide approach150
    FCγRIIASARS-CoVArg131His (no known function) associated with increased disease severity357
    HLARSVNo association145
IVIncreased frequency of HLA-DRB1*07 and decreased frequency of HLA-DQB1*0603-9/14 and DRB1*13 in nonresponders to IV subunit vaccine107
SARS-CoVAssociation of HLA-B*4601 with severity of SARS infection201
    ICAM1RSVNo association178
    ICAM3SARS-CoVAsp143Gly (no known function) associated with decreased white blood cell counts50
    IL4RARSVGln551Arg, which may affect STAT6 binding; associated with increased RSV hospitalization130
    MBLRSVNo association175
SARS-CoVLow-expression polymorphisms associated with SARS infection360
No association357
Higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects144
    TLR4RSVAsp299Gly and Thr399Ile, which reduce TLR4 translocation, associated with severe RSV bronchiolitis322
Asp259Gly increased risk of RSV infection269
Asp299Gly and Thr399Ile were significantly overrepresented among infants with severe RSV bronchiolitis18
No association143, 253
    VCAM1RSVNo association178
    Vitamin D receptorRSVFokI ff genotype, which reduces receptor expression associated with increased rates of ARI281
Thr1Met association on limited genome-wide approach150
Others
    FGL2SARS-CoVGly57Gln (no known function) associated with increased nasal shedding54
    JUNRSV−750G/A allele (no known function) association on limited genome-wide approach150
    L-Sign (CD209L)SARS-CoVNo association197
Homozygous expression of tandem repeats in CLEC4M may bind virus to cells and has a protective advantage51
    MASP2SARS-CoVNo association346
    NOS2ARSV−2757A allele (no known function) association on limited genome-wide approach150
    SP-ARSVGln223Lys, which may alter RSV binding, associated with severe RSV infection206
    SP-BRSVNo association268
    SP-CRSVNo association272
    SP-DRSVNo association177
Met11Thr, which may reduce opsonization, associated with increased risk of RSV bronchiolitis183
  • a The table shows genes that have been studied in association with an increased risk or severity of respiratory viral infection. Many of the studies were not specific for infantile bronchiolitis, but due to the limited availability of published genetic study data, they have also been included here. Where known or speculated, the allele and its putative function have been included. Abbreviations: SNP, single nucleotide polymorphisms; OM, otitis media; ARI, acute respiratory illness; URTI, upper respiratory tract infection; LRTI, lower respiratory tract infection; TGF-β, transforming growth factor β; MBL, mannose binding lectin.