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PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline

PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline
PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline
Background: several studies have suggested that chromosome 19q13.1-3 contains asthma susceptibility genes.
Objective: linkage and association analyses using 587 United Kingdom and Dutch asthma families (n = 2819 subjects) were used to investigate this region.
Methods: a 3-phase procedure was used: (1) linkage and association analyses using 15 microsatellite markers spanning 14.4 mega base pairs (Mbps) on 19q13, (2) fine mapping of the refined region using 26 haplotype tagging single nucleotide polymorphisms (SNPs), and (3) dense gene analyses using 18 SNPs evaluated for association with asthma, bronchial hyperresponsiveness (BHR), FEV1, plasma urokinase plasminogen activator receptor (PLAUR), and rate of annual FEV1 decline in subjects with asthma.
Results: the microsatellite analyses provided tentative support for an asthma/lung function susceptibility locus (48.9-49.1Mbps), and fine mapping localized modest association to the PLAUR gene. PLAUR SNPs in the 5? region, intron 3, and 3? region are associated with asthma and BHR susceptibility and predict FEV1 and plasma PLAUR levels. SNPs in the 5? region showed association for asthma (2 populations), FEV1 (2 populations), and BHR (2 populations) phenotypes. SNPs in intron 3 showed association with asthma (2 populations) and BHR (3 populations). Importantly, the same 5? region and intron 3 SNPs were associated with plasma PLAUR levels. The same 5? region and 3? region SNPs were found to be determinants of FEV1 decline in subjects with asthma.
Conclusion: this study represents the first report to identify PLAUR as a potential asthma susceptibility gene and determine PLAUR regions underlying this association, including a role in influencing plasma PLAUR levels. Finally, the association of PLAUR with lung function decline supports a role for PLAUR in airway remodeling in asthma
asthma, susceptibility, PLAUR, remodeling
0091-6749
1391-1400
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Koppelman, Gerard H.
8d04aab8-5795-4e62-b64a-de7e368c0d1d
Vonk, Judith M.
505c8bc4-909f-40b7-b3ae-1e94aeccc25d
Browning, Claudia A.
95bcab7e-98f6-4e80-b51e-baad1bb5f0b4
Nolte, Ilja M.
2d1a4ad0-9042-44f3-bd9d-768ee280f58d
Stewart, Ceri E.
39812638-540b-4ecf-97bf-b763c826c8b5
Bainbridge, Sue
8662132d-1a8f-461f-ad0e-8f140ddd8aa5
Mutch, Stacey
34c67122-d130-4f1e-91c6-08ec8443d354
Rose-Zerilli, Matthew J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Postma, Dirkje S.
23c1567d-a264-48a1-9ab4-01beda374e42
Maniatis, Nikolas
369fb005-aae0-4243-807b-b42af088debd
Henry, Amanda P.
559d5750-a9f2-4909-875d-33d36f577d63
Hall, Ian P.
744f8a77-0d2f-49a5-a01a-f9f801fe6d24
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Tighe, Patrick
bfa334dd-64d3-48c0-8f4f-87a10cfbc893
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Koppelman, Gerard H.
8d04aab8-5795-4e62-b64a-de7e368c0d1d
Vonk, Judith M.
505c8bc4-909f-40b7-b3ae-1e94aeccc25d
Browning, Claudia A.
95bcab7e-98f6-4e80-b51e-baad1bb5f0b4
Nolte, Ilja M.
2d1a4ad0-9042-44f3-bd9d-768ee280f58d
Stewart, Ceri E.
39812638-540b-4ecf-97bf-b763c826c8b5
Bainbridge, Sue
8662132d-1a8f-461f-ad0e-8f140ddd8aa5
Mutch, Stacey
34c67122-d130-4f1e-91c6-08ec8443d354
Rose-Zerilli, Matthew J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Postma, Dirkje S.
23c1567d-a264-48a1-9ab4-01beda374e42
Maniatis, Nikolas
369fb005-aae0-4243-807b-b42af088debd
Henry, Amanda P.
559d5750-a9f2-4909-875d-33d36f577d63
Hall, Ian P.
744f8a77-0d2f-49a5-a01a-f9f801fe6d24
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Tighe, Patrick
bfa334dd-64d3-48c0-8f4f-87a10cfbc893
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786

Barton, Sheila J., Koppelman, Gerard H., Vonk, Judith M., Browning, Claudia A., Nolte, Ilja M., Stewart, Ceri E., Bainbridge, Sue, Mutch, Stacey, Rose-Zerilli, Matthew J., Postma, Dirkje S., Maniatis, Nikolas, Henry, Amanda P., Hall, Ian P., Holgate, Stephen T., Tighe, Patrick, Holloway, John W. and Sayers, Ian (2009) PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline. Journal of Allergy and Clinical Immunology, 123 (6), 1391-1400. (doi:10.1016/j.jaci.2009.03.014).

Record type: Article

Abstract

Background: several studies have suggested that chromosome 19q13.1-3 contains asthma susceptibility genes.
Objective: linkage and association analyses using 587 United Kingdom and Dutch asthma families (n = 2819 subjects) were used to investigate this region.
Methods: a 3-phase procedure was used: (1) linkage and association analyses using 15 microsatellite markers spanning 14.4 mega base pairs (Mbps) on 19q13, (2) fine mapping of the refined region using 26 haplotype tagging single nucleotide polymorphisms (SNPs), and (3) dense gene analyses using 18 SNPs evaluated for association with asthma, bronchial hyperresponsiveness (BHR), FEV1, plasma urokinase plasminogen activator receptor (PLAUR), and rate of annual FEV1 decline in subjects with asthma.
Results: the microsatellite analyses provided tentative support for an asthma/lung function susceptibility locus (48.9-49.1Mbps), and fine mapping localized modest association to the PLAUR gene. PLAUR SNPs in the 5? region, intron 3, and 3? region are associated with asthma and BHR susceptibility and predict FEV1 and plasma PLAUR levels. SNPs in the 5? region showed association for asthma (2 populations), FEV1 (2 populations), and BHR (2 populations) phenotypes. SNPs in intron 3 showed association with asthma (2 populations) and BHR (3 populations). Importantly, the same 5? region and intron 3 SNPs were associated with plasma PLAUR levels. The same 5? region and 3? region SNPs were found to be determinants of FEV1 decline in subjects with asthma.
Conclusion: this study represents the first report to identify PLAUR as a potential asthma susceptibility gene and determine PLAUR regions underlying this association, including a role in influencing plasma PLAUR levels. Finally, the association of PLAUR with lung function decline supports a role for PLAUR in airway remodeling in asthma

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More information

Published date: June 2009
Keywords: asthma, susceptibility, PLAUR, remodeling
Organisations: Human Genetics, Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 69840
URI: https://eprints.soton.ac.uk/id/eprint/69840
ISSN: 0091-6749
PURE UUID: 8d31d3a7-c0fc-49ce-947b-021e021609c9
ORCID for Sheila J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Matthew J. Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 08 Dec 2009
Last modified: 06 Jun 2018 12:59

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Contributors

Author: Gerard H. Koppelman
Author: Judith M. Vonk
Author: Claudia A. Browning
Author: Ilja M. Nolte
Author: Ceri E. Stewart
Author: Sue Bainbridge
Author: Stacey Mutch
Author: Dirkje S. Postma
Author: Nikolas Maniatis
Author: Amanda P. Henry
Author: Ian P. Hall
Author: Patrick Tighe
Author: Ian Sayers

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