Association of the HTR2A gene with alcohol and heroin abuse

Abstract

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.

Hierarchical investigation of genetic influences on response inhibition in healthy young adults.

“…Importantly, serotonin’s role in inhibition has been previously implicated in increased risk for drug abuse (Cunningham & Anastasio, 2014; Kirby, Zeeb, & Winstanley, 2011). In line with this, the minor allele of rs6313 in HTR2A (identified in this study as predictive of better response inhibition) was associated with less risk for relapse in alcohol dependent individuals (Jakubczyk et al, 2013), and a recent meta-analysis reported that the minor allele was protective across studies of opioid and alcohol abuse and dependence (Cao et al, 2014). Although necessarily speculative, taken together these findings suggest that the association between HTR2A and risk for drug abuse could be due in part to genetic influence on inhibitory control.…”

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

“…Numerous studies have identified a number of single nucleotide polymorphisms that are associated with alcohol dependence and/or drug codependence including (a) CHRM2 (Luo et al, 2005; Wang et al, 2004), CHRNA4 (Kim et al, 2004), CHRNA5 (Saccone et al, 2007; Wang et al, 2009) as well as the CHRNA5-CHRNA3-CHRNB4 cluster and alcohol abuse/dependence (Schlaepfer et al, 2008); (b) DAT (Heinz, Goldman, Gallinat, Schumann, & Puls, 2004; see also Bhaskar & Kumar, 2014 for this and other DA-associated polymorphisms), DA beta hydroxylase (DBH) and alcohol dependence in women (Preuss et al, 2013), DRD3 and alcohol craving (Agrawal et al, 2013) as well as DA dysfunction and Cloninger Type I alcoholism (Leggio & Addolorato, 2008); (c) GABRA1, GABRA2, GABRB3, GABRG3 and alcohol dependence or sensitivity to its intoxicating effects during the ascending slope of the BAC curve (e.g., Bierut et al, 2010; Dick et al, 2004; Dick et al, 2006; Edenberg et al, 2004; Enoch, Schwartz, Albaugh, Virkkunen, & Goldman, 2006; Haughey et al, 2008; Noble et al, 1998); (d) GRIK3 (Grzywacz, Malecka, Suchanecka, Bienkowski, Samochowiec, 2013) and GRIN2A (Domart et al, 2012) with alcohol dependence as well as GRM8 and event-related potential (ERP) theta power and alcohol dependence (Chen et al, 2009); (e) 5HT dysfunction and Cloninger Type II alcoholism (Leggio & Addolorato, 2008), HTR1A and alcohol as well as nicotine co-dependence (Zuo et al, 2013), HTR1B and alcohol as well as multiple drug abuse (Cao, LaRocque, & Li, 2013; Contini et al, 2012), HTR2A and alcohol as well as heroin abuse (Cao et al, 2014), HTR7 and alcohol dependence as wel as electrophysiological measures (Zlojutro et al, 2010; Zuo et al, 2014), alcohol dependence and SERT (e.g., Heinz et al, 2004; c.f., Johnson, 2010; McHugh, Hofman, Asnaani, Sawyer, & Otto, 2010; Plemenitas et al, 2015); (f) OPRM1 and level of response to ethanol in Native Americans (Ehlers, Lind, & Wilhelmsen, 2008), OPRM1 polymorphisms and naltrexone’s efficacy for treating alcohol dependence (e.g., Jonas et al, 2014), as well as PDYN and OPRK1 with alcohol dependence (Gerra et al, 2007; Williams et al, 2007; Xuei et al, 2006); (g) CRFR1 polymorphism with P3 ERP and alcohol dependence (Chen et al, 2010); and (h) NPY and its receptor’s association with alcohol as well as multiple drug abuse and dependencies (Bhaskar et al, 2013; Frances et al, 2011; Okahisa et al, 2009; Sato et al, 2010; Wether...…”

Association between serotonin transporter gene polymorphisms and heroin dependence: a meta-analytic study

“…In the last few years, many studies have reported that association between heroin abuse and serotonin gene,18,19 but the evidence remains inconclusive. Some of them showed the association with 10-repeat allele in STin2 20 or with SS genotype in 5-httlpr ,21 but these positive findings were not replicated in other studies.…”