Dataset Information

Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

ABSTRACT: Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples.

SUBMITTER: Cao J

PROVIDER: S-EPMC4089973 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

Cao Jian J LaRocque Emily E Li Dawei D

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20130117 2

Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To cla ...[more]

PMID: 23335468

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Project description:BACKGROUND:The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. METHODS:Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. RESULTS:Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from -?1587 to -?1371?bp (TSS, +?1), -?1149 to -?894?bp, -?39 to +?130?bp, +?130 to +?341?bp, and?+?341 to +?505?bp upregulated gene expression. In contrast, regions -?603 to -?316?bp and?+?130 to +?341?bp downregulated gene expression. Region +?341 to +?505?bp played a decisive role in gene transcription. CONCLUSIONS:HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region +?341?~?+?505?bp. Regions -?1587 to -?1371?bp, -?1149 to -?894?bp, -?603 to -?316?bp, -?39 to +?130?bp, and?+?130 to +?341?bp contain functional sequences that can promote or suppress the HTR1B gene expression.

Dataset Information

Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

Publications

Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

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