title: Association of asthma with a functional promoter polymorphism in the IL16 gene.
abstract: BACKGROUND
  IL-16, a multifunctional cytokine with increased expression in the airways of asthmatic subjects, inhibits allergic airway inflammation in animal models. A T-->C single nucleotide polymorphism (SNP) at the -295 position in the promoter region of the IL16 gene has been described.
  
  
  OBJECTIVE
  We sought to examine the functional significance of this promoter SNP and its relationship to asthma.
  
  
  METHODS
  We examined the effect of the -295 SNP on promoter activity in cell-line (HBE4-E6/E7) transfection experiments. We investigated the association of the IL16 -295 genotype with asthma among 341 affected sib-pair white families and 184 unrelated nonasthmatic control subjects. We analyzed the association between the IL16 genotype and asthma using family-based association test and case-control analyses.
  
  
  RESULTS
  In in vitro transfection experiments the T allele in the -295 position was associated with substantially reduced promoter activity compared with the C allele. In the family study the more common T allele at the -295 position was significantly associated with all asthma phenotypes (P = .002 to P = .015). In the case-control analysis asthmatic subjects were more likely than unrelated nonasthmatic control subjects to have the -295 TT genotype, but this did not reach statistical significance (odds ratio, 1.36; 95% CI, 0.92-2.02).
  
  
  CONCLUSIONS
  The T allele at the -295 position in the IL16 promoter region is associated with reduced promoter activity relative to the C allele and with asthma in this white population. Further investigation is needed to delineate the mechanisms underlying these findings and the relationship of the IL16 -295 genotype to asthma in other populations.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Burkart
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Barton
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
authors.forename: Julie A
authors.initials: JA
authors.lastname: Cakebread
authors.forename: William
authors.initials: W
authors.lastname: Cruikshank
authors.forename: Frederic
authors.initials: F
authors.lastname: Little
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Jin
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Clough
authors.forename: Tim P
authors.initials: TP
authors.lastname: Keith
authors.forename: Stephen
authors.initials: S
authors.lastname: Holgate
authors.forename: David M
authors.initials: DM
authors.lastname: Center
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D019410:Interleukin-16 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014162:Transfection
chemical_list: D019410:Interleukin-16