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The association of Single Nucleotide Polymorphisms of PPARGC1B with AHR in asthmatic patients

PPARGC1B is a co‐activator for ER, PPAR, and GR, which are involved in asthma development. We investigated the genetic association of PPARGC1B polymorphisms with the risk of asthma and subphenotypes and the functional effect of these polymorphisms on the expression of PPARGC1B. Through direct DNA sequencing for PPARGC1B on chromosome 5q33 of 24 Koreans, we identified 18 polymorphisms. Among them, we choose 7 SNPs for large‐scale genotyping in Korean considering the location of SNPs, MAF and LD. In spite of the lack of association of SNPs with the risk of asthma, we found that −427C>T on promoter and +102525G>A on exon 5 of PPARGC1B were associated with airway hyperreactivity in asthmatics. LogPC20 values of C allele homozygotes on −427C>T was higher than of T allele homozygotes (p=0.004) and A allele homozygotes on +102525G>A was higher than of others (p=0.0001). Using Luciferase reporter system and Gel shift assay, we revealed that −427C type caused higher promoter activity than −427T type. In addition, we identified that B cells possessing −427C presented higher mRNA expression than that having −427T. These results suggest that the polymorphisms of PPARGC1B may affect on the promoter activity followed by development of airway hyperreactivity and the analysis for genotypes on PPARGC1B may be a genetic marker for severity of asthma. This study was supported by a grant of the Korean Health 21 R&D project.