An Association Study Between Alcoholism and the Serotonergic Receptor Genes

Himei, Akio; Kono, Yoshihiro; Yanagawa, Hiroshi; Sakai, Toshiaki; Koh, Jun Sung; Sakai, Jun; Inada, Yasushi; Imamichi, Hiroyuki

doi:10.1097/00000374-200003000-00014

Cited by 8 publications

(8 citation statements)

References 8 publications

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“…These studies were then filtered to ensure conformity with the inclusion criteria. One study (Himei and others 2000) was excluded because it was investigating the 294-Rsa1 polymorphism, rather than the polymorphisms analyzed in this meta-analysis. In the end, 18 studies, composed of 17 case-control (Cao and others 2011; Cigler and others 2001; Contini and others 2012; Gao and others 2011; Hasegawa and others 2002; Lee and others 2009; Proudnikov and others 2006; Sander and others 2000; Sun and others 2002; Ujike and others 2011; Wang and others 2012; Yuan and others 2005) and one HRR study (Hill and others 2002), met our criteria for inclusion.…”

Section: Resultsmentioning

confidence: 99%

Associations of the 5‐hydroxytryptamine (serotonin) Receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse

Cao

LaRocque

2013

American J of Med Genetics Pt B

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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 = 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 odds ratio = 1.42 (1.14, 1.76) and P = 0.01 with odds ratio = 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.

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Section: Resultsmentioning

confidence: 99%

Associations of the 5‐hydroxytryptamine (serotonin) Receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse

Cao

LaRocque

2013

American J of Med Genetics Pt B

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“…Finally, 21 studies, composed of 20 case-control studies and one HRR study (Hill et al 2002), met our criteria for inclusion. The 21 studies included five studies for European populations (Fehr et al 2001; Hill et al 2002; Parsian and Cloninger 2001; Wrzosek et al 2012), two studies for Hispanic samples (Polina et al 2009; Saiz et al 2008), and 14 studies for Asian populations (Cao et al 2002; Gao et al 2011; Himei et al 2000; Hwu and Chen 2000; Lee et al 2009; Li et al 2002; Nakamura et al 1999; Shao et al 2005; Terayama et al 2003; Tsunoka et al 2010; Wang et al 2001; Yang et al 2010). Among these studies, eight studies (Cao et al 2002; Gao et al 2011; Li et al 2002; Saiz et al 2008; Shao et al 2005; Wang et al 2001; Yang et al 2010) investigated heroin dependence or abuse; one study (Tsunoka et al 2010) investigated methamphetamine dependence; and the other 12 studies (Fehr et al 2001; Hill et al 2002; Himei et al 2000; Hwu and Chen 2000; Lee et al 2009; Nakamura et al 1999; Parsian and Cloninger 2001; Polina et al 2009; Terayama et al 2003; Wrzosek et al 2012) investigated alcohol dependence or abuse.…”

Section: Resultsmentioning

confidence: 99%

Association of the HTR2A gene with alcohol and heroin abuse

et al. 2013

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Positive genetic associations of rs6313 (102T/C at exon 1) and rs6311 (-1438A/G) on the 5-hydroxytryptamine (serotonin) 2A receptor gene (HTR2A or 5-HT2A) were reported for alcohol and drug abuse, however, other association studies failed to produce consistent results supporting the susceptibility of the two single nucleotide polymorphisms (SNPs). To clarify the associations of the HTR2A gene with substance use disorders, we performed a meta-analysis based on the genotypes from the available candidate gene association studies of the two SNPs with alcohol and drug abuse from multiple populations. Evidence of association was found for HTR2A rs6313 in all the combined studies (e.g., allelic P = 0.0048 and OR = 0.86, 95% CI 0.77 – 0.95) and also in the combined studies of alcohol dependence (abuse) (e.g., allelic P = 0.0001 and OR = 0.71, 95% CI 0.59 – 0.85). The same association trend was also observed in the SAGE (Study of Addiction: Genetics and Environment) datasets. The meta-analysis supports a contribution of the HTR2A gene to the susceptibility to substance use disorders, particularly alcohol dependence.

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“…The same study was unable to detect any association between rs6318 and AD or alcohol abuse 72. Subsequently, the association between rs6318 and MHPG was not replicated,73 and several other studies failed to find a relationship between rs6318 and AD 61,74. Mottagui-Tabar et al (2004) reported that none of the four HTR2C promoter SNPs investigated nor the promoter microsatellite were shown to be associated with AD 75…”

Section: Htr2c and Substance Use Disordersmentioning

confidence: 97%

Polymorphisms of the serotonin transporter and receptor genes: susceptibility to substance abuse

Herman

Balogh²

2012

SAR

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Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter implicated in regulating substance-use disorder (SUD) acquisition, maintenance, and recovery. During the past several years, an abundance of research has begun discovering and describing specific 5-HT genetic polymorphisms associated with SUDs. Genetic variations in the 5-HT system, such as SLC6A4, HTR1B, HTR2A, HTR2C, HTR3 (HTR3A, HTR3B, HTR3C, HTR3D, and HTR3E), likely play a role contributing to SUD patient heterogeneity. The 5-HT transporter-linked polymorphic region S allele, located in SLC6A4, has now been modestly associated with alcohol dependence in two large meta-analyses. Additional 5-HT genes may also play a role but have not been extensively investigated. A limited number of SUD treatment studies have included 5-HT gene variation as moderating treatment outcomes, but the results have been equivocal. Future research on 5-HT addiction genetics should adopt whole-genome sequencing technology, utilize large study samples, and collect data from multiple ethnic groups. Together, these methods will build on the work already conducted with the aim of utilizing 5-HT genetics in SUD treatment settings.

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An Association Study Between Alcoholism and the Serotonergic Receptor Genes

Abstract: The study results suggest that these serotonergic receptor genes may not directly contribute to the etiology of alcoholism.

Cited by 8 publications

References 8 publications

Associations of the 5‐hydroxytryptamine (serotonin) Receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse

Associations of the 5‐hydroxytryptamine (serotonin) Receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse

Association of the HTR2A gene with alcohol and heroin abuse

Polymorphisms of the serotonin transporter and receptor genes: susceptibility to substance abuse

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