Genome-wide association study identifies ALLC polymorphisms correlated with FEV1 change by corticosteroid

초록

Objectives: Asthma can be suppressed by inhaled corticosteroids (ICS). However, response to ICS shows marked inter-individual variability. This study is aimed to identify the genetic variants associated with the change in the percentage of forced expiratory volume in 1 second (%Delta FEV1) following ICS treatment. Methods: A genome-wide association study was performed in a Korean asthmatic cohort. To further investigate these genetic associations, 11 additional single-nucleotide polymorphisms (SNPs) on the allantoicase (ALLC) gene were selected from the HapMap database and genotyped in the same asthmatic patients in the follow-up study. Results: In a genome-wide study, we identified the lowest P-value in ALLC, but none of the SNPs met the genome-wide association criteria (P < 1.0 x 10(-8)). However, among 25 SNPs on ALLC in the follow-up study, 6 variants showed significant associations with the mean %Delta FEV1 in the study subjects (P < 3.73 x 10(-6)). Conclusions: Although the associated signals could not overcome the genome-wide multiple correction due to small sample size (n = 189), our results suggest that associated SNPs of ALLC might be genetic predictors of response to ICS, at least with respect to Delta FEV1 in Korean asthmatics. (C) 2014 Elsevier B.V. All rights reserved.

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