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

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• 作者：Xingnan Li PhD ; MS^a ; Timothy D. Howard PhD^a ; Wendy C. Moore MD^a ; Elizabeth J. Ampleford PhD^a ; Huashi Li MS^a ; William W. Busse MD^b ; William J. Calhoun MD^c ; Mario Castro MD^d ; Kian Fan Chung MD^e ; Serpil C. Erzurum MD^f ; Anne M. Fitzpatrick PhD^g ; Benjamin Gaston MD^h ; Elliot Israel MDⁱ ; Nizar N. Jarjour MD^j ; W. Gerald Teague MD^h ; Sally E. Wenzel MD^k ; Stephen P. Peters MD ; PhD^a ; Gregory A. Hawkins PhD^a ; Eugene R. Bleecker MD^a ; Deborah A. Meyers PhD^a ; ^{dmeyers@wfubmc.edu"" rel=""nofollow}
• 关键词：Asthma ; genetics ; asthma severity ; meta-analysis ; FEV₁ ; FVC ; FEV₁/FVC ; HHIP ; FAM13A ; PTCH1
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：June 2011
• 年：2011
• 卷：127
• 期：6
• 页码：1457-1465
• 全文大小：924 K

文摘

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 [ppFEV₁] 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.