Genomewide Association between GLCCI1 and Response to Glucocorticoid Therapy in Asthma

• Published in: The New England journal of medicine Vol. 365; no. 13; pp. 1173 - 1183
• Main Authors: Tantisira, Kelan G, Lasky-Su, Jessica, Harada, Michishige, Murphy, Amy, Litonjua, Augusto A, Himes, Blanca E, Lange, Christoph, Lazarus, Stephen C, Lazarus, Ross, Sylvia, Jody, Klanderman, Barbara, Duan, Qing Ling, Qiu, Weiliang, Hirota, Tomomitsu, Martinez, Fernando D, Mauger, David, Sorkness, Christine, Szefler, Stanley, Lemanske, Robert F, Peters, Stephen P, Lima, John J, Nakamura, Yusuke, Tamari, Mayumi, Weiss, Scott T
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 29.09.2011
• Subjects: Adult; Algorithms; Alleles; Alzheimer's disease; Asthma; Asthma - drug therapy; Asthma - genetics; Biological and medical sciences; Child; Chronic obstructive pulmonary disease, asthma; Clinical trials; Female; Forced Expiratory Volume - genetics; Gene mapping; General aspects; Genome-Wide Association Study; Genotype; Glucocorticoids; Glucocorticoids - therapeutic use; Humans; Laboratories; Linkage Disequilibrium; Male; Medical sciences; Patients; Pneumology; Polymorphism, Single Nucleotide; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Respiratory function; Single-nucleotide polymorphism; Transcription; Medicine; Lung disease; Association; Treatment; Respiratory disease; Bronchus disease; Obstructive pulmonary disease; Glucocorticoid; Asthma
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0911353

Patients with asthma vary markedly in their clinical response to inhaled glucocorticoids. These investigators used a novel approach to identify a common variant in the glucocorticoid-induced transcript 1 gene associated with a decreased response to glucocorticoids. Asthma is a complex genetic syndrome that affects 300 million persons worldwide. 1 The response to treatment is also genetically complex and is characterized by high intraindividual repeatability 2 and high interindividual variability, 3 with up to 40% of patients with asthma having no response to therapy. Inhaled glucocorticoids are the most widely prescribed medications for controlling asthma. Levels of endogenous glucocorticoids are heritable and vary, both at baseline and in response to environmental perturbation. 4 – 6 Moreover, studies in families with conditions other than asthma have shown both familial segregation and heritability in responses to glucocorticoid medications. 7 , 8 Given the heritability within the . . .