Korean J Intern Med.  2013 Nov;28(6):708-714. 10.3904/kjim.2013.28.6.708.

A polymorphism in the histone deacetylase 1 gene is associated with the response to corticosteroids in asthmatics

• Kim MH
• Kim SH
• Kim YK
• Hong SJ
• Min KU
• Cho SH
• Park HW

• KMID: 1780132
• DOI: http://doi.org/10.3904/kjim.2013.28.6.708

Abstract

BACKGROUND/AIMS
Recent investigations suggest that histone deacetylase 1 (HDAC1) and HDAC2 may be target molecules to predict therapeutic responses to corticosteroids. We evaluated the effects of variation in HDAC1 and HDAC2 on the response to corticosteroids in asthmatics.
METHODS
Two single nucleotide polymorphisms (SNPs) were selected after resequencing HDAC1 and HDAC2. For the first analysis, we evaluated the association between those SNPs and asthma severity in 477 asthmatics. For the second analysis, we evaluated the effects of these SNPs on lung function improvements in response to corticosteroid treatment in 35 independent adult asthmatics and 70 childhood asthmatics.
RESULTS
We found that one SNP in HDAC1 (rs1741981) was significantly related to asthma severity in a recessive model (corrected p = 0.036). Adult asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower % forced expiratory volume in 1 second (%FEV1) increases in response to systemic corticosteroids treatment compared with the heterozygotes or those homozygous for the major allele (12.7% +/- 7.2% vs. 37.4% +/- 33.7%, p = 0.018). Similarly, childhood asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower %FEV1 increases in response to inhaled corticosteroid treatment compared with the heterozygotes or those homozygous for the major allele (14.1% +/- 5.9% vs. 19.4% +/- 8.9%, p = 0.035).
CONCLUSIONS
The present study demonstrated that rs1741981 in HDAC1 was significantly associated with the response to corticosteroid treatment in asthmatics.

Keyword

Asthma; Glucocorticoids; Histone deacetylase 1; Pharmacogenomics; Polymorphism

MeSH Terms

Administration, Inhalation
Adrenal Cortex Hormones/administration & dosage/*therapeutic use
Adult
Aged
Anti-Asthmatic Agents/administration & dosage/*therapeutic use
Asthma/diagnosis/*drug therapy/enzymology/genetics/physiopathology
Child
Female
Forced Expiratory Volume
Gene Frequency
Heterozygote
Histone Deacetylase 1/*genetics
Histone Deacetylase 2/genetics
Homozygote
Humans
Lung/*drug effects/physiopathology
Male
Middle Aged
Pharmacogenetics
Phenotype
*Polymorphism, Single Nucleotide
Recovery of Function
Severity of Illness Index
Treatment Outcome
Adrenal Cortex Hormones
Anti-Asthmatic Agents
Histone Deacetylase 1
Histone Deacetylase 2