Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants.
The aim of this study was to assess whether prematurely born infants have a genetic predisposition to respiratory syncytial virus (RSV) infection-related respiratory morbidity. One hundred and forty-six infants born at less than 36 weeks of gestation were prospectively followed. Nasopharygeal aspirates were obtained on every occasion the infants had a lower respiratory tract infection (LRTI) regardless of need for admission. DNA was tested for 11 single-nucleotide polymorphisms (SNPs). Chronic respiratory morbidity was assessed using respiratory health-related questionnaires, parent-completed diary cards at a corrected age of 1 year and review of hospital notes. Lung function was measured at a post menstrual age (PMA) of 36 weeks and corrected age of 1 year. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36-week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (interleukin 10 (IL10), nitric oxide synthase 2A (NOS2A), surfactant protein C (SFTPC), matrix metalloproteinase 16 (MMP16) and vitamin D receptor (VDR)) and reduced lung function at 1 year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs.


CONCLUSIONS
Our results suggest that prematurely born infants may have a genetic predisposition to RSV LRTIs and subsequent respiratory morbidity which is independent of premorbid lung function.
Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
Simon B
SB
Drysdale
Michael
M
Prendergast
Mireia
M
Alcazar
Theresa
T
Wilson
Melvyn
M
Smith
Mark
M
Zuckerman
Simon
S
Broughton
Gerrard F
GF
Rafferty
Sebastian L
SL
Johnston
Hennie M
HM
Hodemaekers
Riny
R
Janssen
Louis
L
Bont
Anne
A
Greenough
D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000503:physiopathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012129:Respiratory Function Tests; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics*; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000503:physiopathology / Q000821:virology
D004279:DNA, Viral