التفاصيل البيبلوغرافية
| العنوان: |
Genome-Wide Association Analysis in Asthma Subjects Identifies SPATS2L as a Novel Bronchodilator Response. |
| المؤلفون: |
Himes, Blanca E., Xiaofeng Jiang, Ruoxi Hu, Wu, Ann C., Lasky-Su, Jessica A., Klanderman, Barbara J., Ziniti, John, Senter-Sylvia, Jody, Lima, John J., Irvin, Charles G., Peters, Stephen P., Meyers, Deborah A., Bleecker, Eugene R., Kubo, Michiaki, Tamari, Mayumi, Nakamura, Yusuke, Szefler, Stanley J., Lemanske Jr., Robert F., Zeiger, Robert S., Strunk, Robert C. |
| المصدر: |
PLoS Genetics; Jul2012, Vol. 8 Issue 7, Special section p1-10, 10p, 1 Diagram, 3 Charts, 3 Graphs |
| مصطلحات موضوعية: |
BRONCHODILATOR agents, RESPIRATORY obstructions, RNA, CLINICAL trials, MESSENGER RNA |
| مستخلص: |
Bronchodilator response (BDR) is an important asthma phenotype thatmeasures reversibility of airway obstruction by comparing ung function (i.e. FEV1) before and after the administration of a short-acting β2-agonist, the most common rescue medications sed for the treatment of asthma. BDR also serves as a test of β2-agonist efficacy. BDR is a complex trait that is partly under enetic control. A genome-wide association study (GWAS) of BDR, quantified as percent change in baseline FEV1 after dministration of a b2-agonist, was performed with 1,644 non-Hispanic white asthmatic subjects from six drug clinical trials: AMP, LOCCS, LODO, a medication trial conducted by Sepracor, CARE, and ACRN. Data for 469,884 single-nucleotide olymorphisms (SNPs) were used to measure the association of SNPs with BDR using a linear regression model, while adjusting or age, sex, and height. Replication of primary P-values was attempted in 501 white subjects from SARP and 550 white subjects rom DAG. Experimental evidence supporting the top gene was obtained via siRNA knockdown and Western blotting analyses. he lowest overall combined P-value was 9.7E-07 for SNP rs295137, near the SPATS2L gene. Among subjects in the primary nalysis, those with rs295137 TT genotype had amedian BDR of 16.0 (IQR = [6.2, 32.4]), while those with CC or TC genotypes had a median BDR of 10.9 (IQR = [5.0, 22.2]). SPATS2L mRNA knockdown resulted in increased β2-adrenergic receptor levels. Our results uggest that SPATS2L may be an important regulator of β2-adrenergic receptor down-regulation and that there is promise in aining a better understanding of the biological mechanisms of differential response to b2-agonists through GWAS. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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