RESUMO
BACKGROUND: Asthma affects more than 300 million individuals in the world. Several studies have demonstrated the importance of the genetic component. The aim of this study is to develop a holistic approach, including genetic, epigenetic, and expression analysis to study the Prostaglandin D2 receptor gene (PTGDR) in asthmatic patients. METHODS: In this study, 637 Caucasian individuals were included. Genetic variants were characterized by sequencing, and haplotype and diplotype combinations were established. Electrophoretic mobility shift assays (EMSAs) were performed with different promoter variants. An epigenetic analysis of PTGDR was for the first time developed by MassArray assays, and gene expression was determined by real-time polymerase chain reaction. RESULTS: The -197T > C (Fisher's P = 0.028) and -613C > T (Fisher's P < 0.001) polymorphisms were found to be significantly associated with allergic asthma and allergy to pollen and mites, respectively. In addition, several haplotype and diplotype combinations were associated with different allergy and asthma phenotypes. The presence of the -613C > T SNP determined variations in the EMSAs. Moreover, consistent differences in the methylation and expression patterns were observed between asthmatic patients and controls determining a 2.34-fold increase of PTGDR gene expression in asthmatic patients. CONCLUSIONS: Genetic combinations described have functional implications in the PTGDR promoter activity by changing the transcription factors affinity that will help characterize different risk groups. The differences observed in the transcription factors affinity and in the methylation pattern bring insight into different transcription regulation in these patients. To the best of our knowledge, this is the first work in which the implication of genetic and epigenetic factors of PTGDR has been characterized pointing to putative therapeutic targets.
