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

Clin Chim Acta. 2014 Sep 25:436:20-6. doi: 10.1016/j.cca.2014.04.023. Epub 2014 May 2.

Abstract

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 1second (%ΔFEV1) 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<1.0×10(-8)). However, among 25 SNPs on ALLC in the follow-up study, 6 variants showed significant associations with the mean %ΔFEV1 in the study subjects (P<3.73×10(-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 ΔFEV1 in Korean asthmatics.

Keywords: ALLC; FEV1; Genome-wide association study; Haplotype; Inhaled corticosteroid; Single-nucleotide polymorphism.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / pharmacology*
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Asthma / drug therapy
  • Asthma / enzymology
  • Asthma / genetics*
  • Asthma / physiopathology*
  • Female
  • Forced Expiratory Volume / drug effects
  • Genome-Wide Association Study*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Ureohydrolases / genetics*
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Ureohydrolases
  • allantoicase