WAKE FOREST UNIVERSITY
Beta-agonists are the most common medication used for treatment of acute asthma attacks. Inter-individual responses to beta-agonist are variable, and there is strong evidence that genetics play an important role in determining these inter-individual responses. The ?2AR gene ADR?2 has been intensely studied, and several ADR?2 genetic variations that affect receptor response to beta-agonist have been identified. Many of these genetic variants have also been clinically evaluated for effects on beta-agonist response resulting in conflicting data on the pharmacogenetic influence of ADR?2 variations. These conflicting results also beg the question whether other regulatory factors affect ADR?2 expression and response to beta-agonist. Epigenetics is the study of changes in gene function and regulation that occur without changing the genetic code. DNA methylation of cytosines in the DNA sequence CpG is the most commonly studied epigenetic effect. In this proposal, we hypothesize that ADR?2 may exist in different methylated states and that these different states of DNA methylation may play an important role in regulating ADR?2 expression. To test this hypothesis, we propose the following two specific aims: 1) Perform methylation specific sequencing on ADR?2 to identify the most common methylated CpG sites; 2) Assess effects DNA methylation on ADR?2 expression. PUBLIC HEALTH RELEVANCE: This proposal will take the first step in answering whether epigenetics can have a potential role in modifying beta agonist response by assessing the degree of methylation occurring in the pharmacogenetic candidate gene ADR?2 and allow us to assess which specific cell type will be most useful for performing future functional studies exploring the effect of ADR?2 methylation on gene expression.