Importance of hedgehog interacting protein and other lung function genes in asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:127

Article

Li, Xingnan¹  Howard, Timothy D.¹  Moore, Wendy C.¹  Ampleford, Elizabeth J.¹  Li, Huashi¹  Busse, William W.²  Calhoun, William J.³  Castro, Mario^4,5  Chung, Kian Fan⁶  Erzurum, Serpil C.⁷  Fitzpatrick, Anne M.⁸  Gaston, Benjamin⁹  Israel, Elliot¹⁰  Jarjour, Nizar N.^11,12  Teague, W. Gerald⁹  Wenzel, Sally E.¹³  Peters, Stephen P.¹  Hawkins, Gregory A.¹  Bleecker, Eugene R.¹  Meyers, Deborah A.¹ 

[1] Wake Forest Univ, Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA

[2] Univ Wisconsin, Dept Med, Madison, WI USA

[3] Univ Texas Med Branch, Dept Internal Med, St Louis, MO USA

[4] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[6] Imperial Coll Sch Med, Dept Resp Med, London, England

[7] Lerner Res Inst, Cleveland, OH USA

[8] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA

[9] Univ Virginia Hlth Syst, Dept Pediat, Charlottesville, VA USA

[10] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA

[11] Univ Wisconsin Hosp & Clin, Dept Med, Madison, WI 53792 USA

[12] Univ Wisconsin Hosp & Clin, Dept Publ Hlth Sci, Madison, WI 53792 USA

[13] Univ Pittsburgh, Pittsburgh, PA USA

关键词: Asthma;    genetics;    asthma severity;    meta-analysis;    FEV1;    FVC;    FEV1/FVC;    HHIP;    FAM13A;    PTCH1;   

DOI  :  10.1016/j.jaci.2011.01.056

来源: Elsevier

【 摘 要 】

Background: Two recent large meta-analyses of genome-wide association studies of lung function in general populations of European descent identified 11 candidate genes/regions. The importance of these genes in lung function in white and African American subjects with asthma is unknown. Objectives: To determine whether genes that regulate lung function in general populations are associated with lung function abnormalities in subjects with asthma from different racial groups. Methods: Single nucleotide polymorphisms (SNPs) were tested in 5 asthma populations (N = 1441) for association with pulmonary function, and meta-analysis was performed across populations. The SNPs with the highest significance were then tested for association with bronchodilator reversibility and bronchial hyperresponsiveness to methacholine. A joint analysis of consistently replicated SNPs was performed to predict lung function in asthma. Results: Hedgehog interacting protein (HHIP) on chromosome 4q31 was associated with lung function in all 5 populations (rs1512288: P-meta = 9.62E-05 and 3.23E-05 for percent predicted FEV1 [ppFEV(1)] and percent predicted forced vital capacity [ppFVC], respectively). The SNPs in HHIP were also associated with reversibility (P < .05) but not bronchial hyperresponsiveness to methacholine. Because of differences in linkage disequilibrium in the African American subjects, the most relevant SNPs in HHIP were identified. A subset of normal lung function genes, including HHIP, family with sequence similarity 13, member A (FAM13A), and patched homolog 1 (PTCH1), together predict lung function abnormalities, a measure of severity in white and African American subjects with asthma. Conclusion: A subset of the genes, including HHIP, that regulate lung function in general populations are associated with abnormal lung function in asthma in non-Hispanic white and African American subjects. (J Allergy Clin Immunol 2011;127:1457-65.)

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