Cross-sectional and longitudinal association of the secretoglobin 1A1 gene A38G polymorphism with asthma phenotype in the Perth Infant Asthma Follow-up cohort

I A Laing, N H De Klerk, S W Turner, P K Judge, C M Hayden, L I Landau, J Goldblatt, P N Le Souef

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

BACKGROUND: Associations between Clara cell secretory protein gene variants (SCGB1A1, also known as CC16, CC10, CCSP and uteroglobin) and the asthma phenotype have been found in five out of eight studies world-wide. No study has investigated the contribution of SCGB1A1 polymorphisms to the development and/or persistence of the asthma phenotype in a birth cohort followed over time.

OBJECTIVE: The aim of this study was to determine the role of the SCGB1A1 gene in the development of the asthma phenotype.

METHODS: The Perth Infant Asthma Follow-up (PIAF) cohort (n=231 unrelated infants, unselected for asthma and recruited at birth) were seen at 1 month, 6 and 11 years of age, and had a questionnaire, lung function, airway responsiveness (AR) and skin prick tests (SPTs) completed. Blood was taken at 6 and 11 years for total and specific immunoglobulin E (sIgE) and DNA extraction. SPT positivity had at least one positive SPT. SIgE>4 kU/L had at least one sIgE above 4 kU/L. SCGB1A1 A38G (rs3741240), that alters gene transcription, was genotyped using Sau96I restriction digestion of exon 1 PCR products.

RESULTS: At 6 and 11 years of age, 33.0% and 29.7% of those genotyped had doctor-diagnosed asthma, and 35.8% and 52.1% had SPT positivity. In cross-sectional analyses, children with 38G/38A or 38A/38A had increased AR at 1 month (1.72-fold, P=0.013); sIgE>4 kU/L [odds ratio (OR)=6.95, 95% confidence interval (CI)=1.35-35.91, P=0.021]; house dust mite (HDM) SPT positivity (OR=7.21, 95% CI=1.09-47.78, P=0.041) and sIgE (4.57-fold, P=0.045) at 6 years; and doctor-diagnosed asthma (OR=3.93, 95% CI=1.24-12.47, P=0.02) and cat SPT positivity (OR=4.34, 95% CI=1.01-18.77, P=0.049) at 11 years. Longitudinal analyses of 6 and 11 years paired data showed that children with 38A/38A had increased persistent sIgE>4 kU/L (OR=11.87, 95% CI=1.97-71.53, P=0.007) and persistent HDM SPT positivity (OR=7.84, 95% CI=1.04-58.92, P=0.045).

CONCLUSION: SCGB1A1 A38G may play a role in the development and persistence of the asthma phenotype in childhood.

Comment in
Secretoglobin 1A1 gene and asthma pre-disposition: what is the evidence? [Clin Exp Allergy. 2009]
Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalClinical & experimental allergy
Volume39
Issue number1
Early online date16 Oct 2008
DOIs
Publication statusPublished - Jan 2009

Keywords

  • airway responsiveness
  • asthma
  • atopy
  • children
  • longitudinal study
  • polymorphism
  • SCGB1A1

Fingerprint

Dive into the research topics of 'Cross-sectional and longitudinal association of the secretoglobin 1A1 gene A38G polymorphism with asthma phenotype in the Perth Infant Asthma Follow-up cohort'. Together they form a unique fingerprint.

Cite this