Serotonin 2A receptor gene (HTR2A) polymorphism in alcohol-dependent patients

Wrzosek, Małgorzata; Jakubczyk, Andrzej; Wrzosek, Michał; Matsumoto, Halina; Łukaszkiewicz, Jacek; Kirk, J Brower; Wojnar, Marcin

doi:10.1016/s1734-1140(12)70787-9

Cited by 21 publications

(5 citation statements)

References 19 publications

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“…The higher frequencies of the C allele and CC genotype in this study likely reflect alcohol dependence. In a study by Wrzosek et al (2012) on a group of 150 alcohol-dependent patients (which is a subsample of our study group), the frequencies of the C allele and CC genotype in the alcohol-dependent group were significantly higher than in controls. Therefore, these studies suggest that the CC genotype is both a marker for alcohol dependence and a risk factor for worse treatment outcome.…”

Section: Discussionmentioning

confidence: 80%

The CC genotype in the T102C HTR2A polymorphism predicts relapse in individuals after alcohol treatment

Jakubczyk

Klimkiewicz

Krasowska

et al. 2013

Journal of Psychiatric Research

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The serotonin system is hypothesized to contribute to predisposition and course of alcohol dependence. However, the potential association between the T102C polymorphism (rs6313) in the type 2A serotonin receptor (HTR2A) gene and treatment outcomes in alcohol dependence has not been investigated. The aim of the study was to assess the contribution of this genetic polymorphism as a predictor of relapse in relation to other previously identified predictors. A sample of 254 alcohol dependent subjects, were recruited in alcohol treatment centers in Warsaw, Poland and prospectively assessed at baseline and follow-up after 12 months. At baseline, information about demographics, psychopathological symptoms and alcohol problems was obtained. The stop-signal task was performed and blood samples for genetic analysis of HTR2A T102C (rs6313) were collected. Relapse was defined as any drinking during the follow-up period. The statistical analysis showed that the CC genotype was significantly associated with increased relapse. Other significant factors were baseline depressive symptoms, number of drinking days during the 3 months prior to the baseline assessment, severity of alcohol-related problems, and a lifetime history of impulsive suicide attempts. Logistic regression analysis with and without the genetic factor revealed that adding the genetic factor increased the R square value by about 4%, with the CC genotype in the T102C polymorphism being the strongest predictor of relapse (OR=2.32). The significant influence on relapse of the CC genotype, which is associated with fewer 5-HT2A receptors in the central nervous system, suggests the possibility that this genetic polymorphism could influence response to serotonergic medications.

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Section: Discussionmentioning

confidence: 80%

The CC genotype in the T102C HTR2A polymorphism predicts relapse in individuals after alcohol treatment

Jakubczyk

Klimkiewicz

Krasowska

et al. 2013

Journal of Psychiatric Research

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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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“…Studies have shown an association between alcoholism and several gene polymorphisms. For example, polymorphisms in the serotonin 2A receptor gene, dopamine transporter, μ-opioid, or GABA A receptor genes have been associated with alcohol dependence (Oslin et al, 2003; Edenberg and Kranzler, 2005; Ramchandani et al, 2011; Bhaskar et al, 2012; Wrzosek et al, 2012). In addition, recent clinical investigation has indicated the CRF1-R locus to mediate genetic susceptibility for excessive drinking (Treutlein et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Role of a Genetic Polymorphism in the Corticotropin-Releasing Factor Receptor 1 Gene in Alcohol Drinking and Seeking Behaviors of Marchigian Sardinian Alcohol-Preferring Rats

et al. 2013

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Marchigian Sardinian alcohol-preferring (msP) rats exhibit innate preference for alcohol, are highly sensitive to stress and stress-induced alcohol seeking. Genetic analysis showed that over-expression of the corticotropin-releasing factor (CRF) system of msP rats is correlated with the presence of two single nucleotide polymorphisms (SNPs) occurring in the promoter region (position −1836 and −2097) of the CRF1 receptor (CRF1-R) gene. Here we examined whether these point mutations were associated to the innate alcohol preference, stress-induced drinking, and seeking. We have recently re-derived the msP rats to obtain two distinct lines carrying the wild type (GG) and the point mutations (AA), respectively. The phenotypic characteristics of these two lines were compared with those of unselected Wistar rats. Both AA and GG rats showed similar patterns of voluntary alcohol intake and preference. Similarly, the pharmacological stressor yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) elicited increased operant alcohol self-administration under fixed and progressive ratio reinforcement schedules in all three lines. Following extinction, yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) significantly reinstated alcohol seeking in the three groups. However, at the highest dose this effect was no longer evident in AA rats. Treatment with the CRF1-R antagonist antalarmin (0, 5, 10, and 20 mg/kg) significantly reduced alcohol-reinforced lever pressing in the AA line (10 and 20 mg/kg) while a weaker or no effect was observed in the Wistar and the GG group, respectively. Finally, antalarmin significantly reduced yohimbine-induced increase in alcohol drinking in all three groups. In conclusion, these specific SNPs in the CRF1-R gene do not seem to play a primary role in the expression of the msP excessive drinking phenotype or stress-induced drinking but may be associated with a decreased threshold for stress-induced alcohol seeking and an increased sensitivity to the effects of pharmacological blockade of CRF1-R on alcohol drinking.

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Serotonin 2A receptor gene (HTR2A) polymorphism in alcohol-dependent patients

Abstract: The results suggest a potential role of the T102C HTR2A polymorphism in development of alcohol dependence.

Cited by 21 publications

References 19 publications

The CC genotype in the T102C HTR2A polymorphism predicts relapse in individuals after alcohol treatment

The CC genotype in the T102C HTR2A polymorphism predicts relapse in individuals after alcohol treatment

Association of the HTR2A gene with alcohol and heroin abuse

Role of a Genetic Polymorphism in the Corticotropin-Releasing Factor Receptor 1 Gene in Alcohol Drinking and Seeking Behaviors of Marchigian Sardinian Alcohol-Preferring Rats

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