Ya-Hui Xu1, Lin-Lin Wang2, Le Shi3, Jin-Ping Lei4, Qin Miao1, Tie-Qiao Liu5, Wei Hao5, Lin Lu3, Rui-Ling Zhang1. 1. a Department of Addiction , Second Affiliated Hospital of Xinxiang Medical University , Xinxiang , Henan Province , China. 2. b Department of Psychology , Ninth People Hospital of Zhengzhou , Zhengzhou , Henan Province , China. 3. c Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health and National Institute on Drug Dependence, Peking University , Beijing , China. 4. d People Hospital of Cangzhou , Cangzhou , Hebei Province , China. 5. e Mental Health Institute, Second Xiangya Hospital, Central South University , Changsha , Hunan Province , China.
Abstract
BACKGROUND: 5-Hydroxytryptamine (5-HT) 3 receptor plays a crucial role in craving of alcohol dependence. Recent evidence shows that chronic alcohol exposure causes changes in gene expression and induces behavioral changes. However, the relationship between gene expression of 5-HT3 receptor and craving in alcohol-dependent patients is not fully understood. OBJECTIVES: The aim of this preliminary study was to investigate the relationship between gene expression of the 5-HT3 receptor and craving in alcohol-dependent patients and the epigenetic mechanism. METHODS: We recruited 50 male Han Chinese alcohol-dependent patients and 46 male Han Chinese healthy controls. We investigated the changes of HTR3A mRNA, which encodes the 5-HT3 receptor A subunit, and H3K9 acetylation in HTR3A promoter region. Obsessive Compulsive Drinking Scale (OCDS) was used to assess the craving of alcohol-dependent patients relative to controls. RESULTS: HTR3A mRNA expression levels and acetylation levels of H3K9 in the HTR3A promoter region were significantly higher in the alcohol-dependent patients. HTR3A mRNA expression levels were positively correlated with OCDS scores. Moreover, HTR3A mRNA expression levels were positively correlated with acetylation levels of H3K9 in HTR3A promoter region. CONCLUSION: The current findings suggest that HTR3A mRNA expression levels were positively correlated with craving in Han Chinese alcohol-dependent patients. The regulation of H3K9 histone acetylation in HTR3A promoter region may offer a target for the treatment of alcohol dependence.
BACKGROUND: 5-Hydroxytryptamine (5-HT) 3 receptor plays a crucial role in craving of alcohol dependence. Recent evidence shows that chronic alcohol exposure causes changes in gene expression and induces behavioral changes. However, the relationship between gene expression of 5-HT3 receptor and craving in alcohol-dependent patients is not fully understood. OBJECTIVES: The aim of this preliminary study was to investigate the relationship between gene expression of the 5-HT3 receptor and craving in alcohol-dependent patients and the epigenetic mechanism. METHODS: We recruited 50 male Han Chinese alcohol-dependent patients and 46 male Han Chinese healthy controls. We investigated the changes of HTR3A mRNA, which encodes the 5-HT3 receptor A subunit, and H3K9 acetylation in HTR3A promoter region. Obsessive Compulsive Drinking Scale (OCDS) was used to assess the craving of alcohol-dependent patients relative to controls. RESULTS:HTR3A mRNA expression levels and acetylation levels of H3K9 in the HTR3A promoter region were significantly higher in the alcohol-dependent patients. HTR3A mRNA expression levels were positively correlated with OCDS scores. Moreover, HTR3A mRNA expression levels were positively correlated with acetylation levels of H3K9 in HTR3A promoter region. CONCLUSION: The current findings suggest that HTR3A mRNA expression levels were positively correlated with craving in Han Chinese alcohol-dependent patients. The regulation of H3K9 histone acetylation in HTR3A promoter region may offer a target for the treatment of alcohol dependence.