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.
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