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Association of asthma with a functional promoter polymorphism in the IL16 gene

Association of asthma with a functional promoter polymorphism in the IL16 gene
Association of asthma with a functional promoter polymorphism in the IL16 gene
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.
asthma, il-16, genetic epidemiology, family-based association test, atopy, single nucleotide polymorphism
0091-6749
86-91
Burkart, Kristin M.
d0df0e00-2039-44aa-8330-a16549d25f3d
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Yang, Ian A.
f55f0532-ce8f-424c-af64-f8052139f2f2
Cakebread, Julie A.
f5aa15da-3462-4809-9e69-eef5d6d2df0d
Cruikshank, William
a4a0327a-888c-45ba-b7fc-9656039e405e
Little, Frederic
347ba4fe-1519-4f8d-8263-e1413b3893cb
Jin, Xiaoyi
af8260bb-dcb1-4c63-a2e6-77bad96dd7ec
Farrer, Lindsay A.
5e0f83bf-3eb9-458a-b750-f1e608499e48
Clough, Joanne B.
34303b05-f47d-4e5d-8763-46628fbe1a8c
Keith, Tim P.
a9d7a544-cc17-4cc7-a12f-71af7b6dfb70
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Center, David M.
1151c776-9c84-4c02-8b83-04089e02b03c
O'Connor, George T.
c3acc8fa-e81a-459f-9ddc-3a3afc9efece
Burkart, Kristin M.
d0df0e00-2039-44aa-8330-a16549d25f3d
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Yang, Ian A.
f55f0532-ce8f-424c-af64-f8052139f2f2
Cakebread, Julie A.
f5aa15da-3462-4809-9e69-eef5d6d2df0d
Cruikshank, William
a4a0327a-888c-45ba-b7fc-9656039e405e
Little, Frederic
347ba4fe-1519-4f8d-8263-e1413b3893cb
Jin, Xiaoyi
af8260bb-dcb1-4c63-a2e6-77bad96dd7ec
Farrer, Lindsay A.
5e0f83bf-3eb9-458a-b750-f1e608499e48
Clough, Joanne B.
34303b05-f47d-4e5d-8763-46628fbe1a8c
Keith, Tim P.
a9d7a544-cc17-4cc7-a12f-71af7b6dfb70
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Center, David M.
1151c776-9c84-4c02-8b83-04089e02b03c
O'Connor, George T.
c3acc8fa-e81a-459f-9ddc-3a3afc9efece

Burkart, Kristin M., Barton, Sheila J., Holloway, John W., Yang, Ian A., Cakebread, Julie A., Cruikshank, William, Little, Frederic, Jin, Xiaoyi, Farrer, Lindsay A., Clough, Joanne B., Keith, Tim P., Holgate, Stephen, Center, David M. and O'Connor, George T. (2006) Association of asthma with a functional promoter polymorphism in the IL16 gene. Journal of Allergy and Clinical Immunology, 117 (1), 86-91. (doi:10.1016/j.jaci.2005.10.011).

Record type: Article

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.

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More information

Published date: January 2006
Keywords: asthma, il-16, genetic epidemiology, family-based association test, atopy, single nucleotide polymorphism

Identifiers

Local EPrints ID: 26974
URI: https://eprints.soton.ac.uk/id/eprint/26974
ISSN: 0091-6749
PURE UUID: 9436cc62-000f-407a-9545-b9b693e200a0
ORCID for Sheila J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 06 Jun 2018 12:59

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