Neuropsychiatric Disease and Treatment (Jan 2019)
The association between HTR1B gene rs13212041 polymorphism and onset of alcohol abuse
Abstract
Dubravka Svob Strac,1 Gordana Nedic Erjavec,1 Matea Nikolac Perkovic,1 Korona Nenadic-Sviglin,2 Marcela Konjevod,1 Mirko Grubor,3 Nela Pivac1 1Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia; 2Center for Alcoholism and other Addictions, University Psychiatric Hospital Vrapce, Zagreb, Croatia; 3Faculty of Pharmacy and Biochemistry University of Zagreb, Zagreb, Croatia Background: Alcohol dependence displays a wide variety of clinical phenotypes. Various typology classifications of alcoholism include age of onset of alcohol abuse as one of the major phenotypic features. Serotonergic changes have been associated with alcoholism, while serotonin receptors type 1B (5-HT1B) play an important role in regulating serotonergic neurotransmission. The rs13212041 polymorphism modulates the expression of HTR1B gene coding for 5-HT1B receptor. This study examined the association of platelet serotonin (5-HT) and HTR1B gene with the onset of alcohol abuse in alcohol-dependent subjects. Materials and methods: Determination of platelet 5-HT concentration and genotyping of rs13212041 HTR1B gene polymorphism were performed in 613 alcohol-dependent patients, subdivided according to early/late onset (before/after 25 years of age) of alcohol abuse. Results: Alcohol-dependent individuals with CC genotype were more frequent in the group with early onset of alcohol abuse compared to carriers of T allele. Besides HTR1B genotype, age and gender, but not platelet 5-HT, were major variables associated with the onset of alcohol abuse. Platelet 5-HT concentration was not significantly different between patients with early and late onset of alcohol abuse, or patients carrying various HTR1B genotypes. Although we observed no influence of co-variables such as age, gender, or somatic and psychiatric comorbidities, platelet 5-HT concentration was significantly affected by smoking. Conclusion: These findings support potential involvement of 5-HT1B receptors in the onset of alcohol abuse and development of alcohol dependence. Additionally, the results of our study emphasize the importance of controlling for smoking status, as one of the significant confounding factors influencing platelet 5-HT concentration. Keywords: alcoholism, age of onset, 5-HT1B, gene variants, platelet serotonin, smoking