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: Kristin M Burkart, Sheila J Barton, John W Holloway, Ian A Yang, Julie A Cakebread, William Cruikshank, Frederic Little, Xiaoyi Jin, Lindsay A Farrer, Joanne B Clough, Tim P Keith, Stephen Holgate, David M Center, George T O'Connor
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 117 Issue 1 Pg. 86-91 (Jan 2006) ISSN: 0091-6749 [Print] United States
• PMID: 16387589 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-16

Topics

• Adolescent
• Adult
• Asthma (genetics)
• Case-Control Studies
• Child
• Female
• Humans
• Interleukin-16 (genetics)
• Male
• Odds Ratio
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic
• Transfection