Association of urokinase-type plasminogen activator with asthma and atopy

被引:38
作者
Begin, Philippe
Tremblay, Karine
Daley, Denise
Lemire, Mathieu
Claveau, Sebastien
Salesse, Charleen
Kacel, Sabine
Montpetit, Alexandre
Becker, Allan
Chan-Yeung, Moira
Kozyrskyj, Anita L.
Hudson, Thomas J.
Laprise, Catherine
机构
[1] Chicoutimi Univ Hosp, Univ Montreal, Community Genom Med Ctr, Saguenay, PQ, Canada
[2] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
[3] Univ Laval, Dept Med, Laval, PQ, Canada
[4] Univ British Columbia, James Hogg iCAPTURE Ctr, Vancouver, BC V5Z 1M9, Canada
[5] McGill Univ, Montreal, PQ, Canada
[6] Genome Quebec Innovat Ctr, Montreal, PQ, Canada
[7] Univ Quebec Chicoutimi, Dept Fundamental Sci, Saguenay, PQ, Canada
[8] Univ Manitoba, Fac Med, Dept Pediat & Child Hlth, Winnipeg, MB, Canada
[9] Manitoba Ctr Hlth Policy, Fac Pharm, Winnipeg, MB, Canada
[10] Manitoba Ctr Hlth Policy, Dept Community Hlth Sci, Winnipeg, MB, Canada
[11] Ontario Inst Canc Res, Toronto, ON, Canada
关键词
airway hyperresponsiveness; association study; asthma; atopy; haplotypes; urokinase-type plasminogen activator gene;
D O I
10.1164/rccm.200607-1012OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale: Urokinase plasminogen activator (uPA) interacts with its receptor on inflammatory and migrating cells to regulate extracellular matrix degradation, cell adhesion, and inflammatory cell activation. It is necessary for the development of an appropriate immune response and is involved in tissue remodeling. The PLAU gene codes for this enzyme, and is located on 10q24. This region has demonstrated evidence for linkage in a genome scan for asthma in a sample from northeastern Quebec. Here, we hypothesized that uPA may function as a regulator of asthma susceptibility. Objectives: To test for association between asthma and genetic variants of PLAU. Methods: We sequenced PLAU and tested for genetic association between identified variants and asthma-related traits in a French-Canadian familial collection (231 families, 1,139 subjects). Additional association studies were performed in two other family-based Canadian cohorts (Canadian Asthma Primary Prevention Study [CAPPS], 238 trios; and Study of Asthma Genes and the Environment [SAGE], 237 trios). Measurements and Main Results: In the original sample, under the dominant model, the common alleles, rs2227564C (P141) and rs2227566T, were associated with asthma (p = 0.011 and 0.045, respectively) and with airway hyperresponsiveness (AHR) (p = 0.026 and 0.038, respectively). Analysis of the linkage disequilibrium pattern also revealed association of the common haplotype for asthma, atopy, and AHR (p = 0.031, 0.043, and 0.006, respectively). Whereas no significant association was detected for PLAU single-nucleotide polymorphisms in the CAPPS cohort, association was observed in the SAGE cohort between the rs4065C allele and atopy under additive (p = 0.005) and dominant (p = 0.0001) genetic models. Conclusions: This suggests a role for the uPA pathway in the pathogenesis of the disease.
引用
收藏
页码:1109 / 1116
页数:8
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