Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 117, Issue 1, Pages 86-91Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2005.10.011
Keywords
asthma; IL-16; genetic epidemiology; family-based association test; atopy; single nucleotide polymorphism
Categories
Funding
- MRC [G19/34] Funding Source: UKRI
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [F32HL074571] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI050516] Funding Source: NIH RePORTER
- Medical Research Council [G19/34] Funding Source: Medline
- NHLBI NIH HHS [HL74571] Funding Source: Medline
- NIAID NIH HHS [AI50516] Funding Source: Medline
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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.
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