Genetic effect of single-nucleotide polymorphisms in the PPARGC1B gene on airway hyperreactivity in asthmatics

Abstract

Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is a co-activator for intracellular receptors such as the ER, PPAR, and GR, which are involved in asthma development. Association of single-nucleotide polymorphisms (SNPs) in PPARGC1B gene with risk of asthma and airway hyperreactivity (AHR) was investigated. Direct sequencing of DNA from 24 Korean was performed to identify PPARGC1B SNPs. Genotyping was done in 264 controls and 949 asthmatics. 19 SNPs were identified, and 7 SNPs were genotyped. No significant difference existed in the distribution between the asthmatics and controls. However, allele frequency of −427C>T showed a significant association with logPC20 methacholine values in the asthmatics (p = 0.005). Real-time PCR demonstrated higher PPARGC1B mRNA levels in asthmatics having the −427CC allele than in those having −427TT or CT alleles. Luciferase reporter assays revealed that −427C allele caused higher promoter activity than −427T allele. EMSA demonstrated that −427C allele exhibited stronger binding activity to a nuclear protein in 293T cells than did the −427T allele. The polymorphisms of −427C>T on the promoter the PPARGC1B gene may affect the development of AHR through the modulation of PPARGC1B gene products.