Association of polymorphisms in HTR2A, HTR1A and TPH2 genes with suicide attempts in alcohol dependence: A preliminary report

Wrzosek, Małgorzata; Łukaszkiewicz, Jacek; Serafin, Piotr; Jakubczyk, Andrzej; Klimkiewicz, Anna; Matsumoto, Halina; Brower, Kirk J.; Wojnar, Marcin

doi:10.1016/j.psychres.2011.04.027

Cited by 38 publications

(24 citation statements)

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“…Similar results have been found in Caucasian subjects with suicide attempts and alcohol dependence [57,58,59]. As for HTR1B rs13212041, we found no association with alcohol dependence.…”

Section: Discussionsupporting

confidence: 90%

Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males

et al. 2015

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Background: Genes involved in the serotonin pathway may determine the susceptibility to alcohol dependence and its severity. The present study explored whether specific polymorphisms in the serotonin pathway could be associated with alcohol dependence or alcohol-related psychopathological symptoms. Methods: The cohort comprised 101 currently and 100 formerly alcohol-dependent males, as well as 97 male healthy blood donors. The following questionnaires were employed: the Alcohol Use Disorders Identification Test, the Zung Depression and Anxiety Scale, the Brief Social Phobia Scale, the Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Drinking Scale, and the Buss-Durkee Hostility Inventory. Subjects were genotyped for bi- and triallelic SLC6A4 5-HTTLPR,HTR1A rs6295, and HTR1B rs13212041. Results: Statistical differences in bi- and triallelic SLC6A4 5-HTTLPR genotype distribution were observed between the 3 groups investigated (p = 0.008 and p = 0.023, respectively); however, no gene-dose effect was observed. The severity of the alcohol problems was higher in currently alcohol-dependent subjects with the 5-HTTLPR LL (p = 0.039) and L′L′ genotypes (p = 0.027). Formerly dependent subjects with the 5-HTTLPR S′S′ genotype showed more social anxiety, depressive, and anxiety traits (p = 0.009, p = 0.006, and p = 0.036, respectively). Healthy controls with the 5-HTTLPR SS genotype showed more traits of social anxiety (p = 0.020). Conclusions: Our findings suggest that bi- and triallelic SLC6A4 5-HTTLPR has some effects on the severity of alcohol dependence. Triallelic 5-HTTLPR was associated with social anxiety, anxiety, and depressive traits in alcohol-dependent subjects.

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“…Similar results have been found in Caucasian subjects with suicide attempts and alcohol dependence [57,58,59]. As for HTR1B rs13212041, we found no association with alcohol dependence.…”

Section: Discussionsupporting

confidence: 90%

Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males

et al. 2015

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“…Rodent animal models and human clinical studies suggest dysfunction in serotonin (5-HT) innervation and transmission in early-onset genetically determined or type 2 alcoholism. A candidate gene association study found an association with variants of HTR1A with suicide attempts in alcohol dependent patients (Wrzosek et al, 2011). A 5HT1A/B antagonist (WAY100635) reduces drug seeking during initial abstinence in rats (Kohtz and Aston-Jones, 2017).…”

Section: Genome-wide Association Studies Of Alcohol Dependencementioning

confidence: 99%

Genetic studies of alcohol dependence in the context of the addiction cycle

et al. 2017

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Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50–60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled “Alcoholism”.

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“…Ряд исследований, проведенных на трансгенных мышах, лишен-ных гена рецептора HTR1B, констатирует возможное вовлечение функци-ональных вариантов гена HTR1B в этиологию таких психических рас-стройств, как агрессивность и алкоголизм (Saudo et al, 1994;Brunner et al, 1999). Ряд независимых исследований подтвердил ассоциацию поли-морфных вариантов гена HTR1B с суицидальным поведением (Gaysina et al, 2003;Lappalainen et al, 1998;New et al, 2001), однако имеются рабо-ты, в которых данная ассоциация не выявлена (Wang et al, 2009;Zupanc et al, 2010;Murphy et al, 2011;Wrzosek et al, 2011).…”

Section: роль генов нейромедиаторных систем мозга в суицидальном повеunclassified

“…Сооб-щалось также, что сигнальная трансдукция через рецепторы HTR2A может быть повреждена в результате альтернативного сплайсинга и измененной структуры белка (Arango et al, 2003). К настоящему времени получены данные, как подтверждающие, так и не подтверждающие ассоциацию гена НТR2А с суицидальным поведением (Гайсина и др., 2008; Gaysina et al, 2003Brezo et al, 2010;Zupanc et al, 2010;Zalsman et al, 2011;Wrzosek et al, 2011).…”

Section: роль генов нейромедиаторных систем мозга в суицидальном повеunclassified

Genetic Research on Sleep, Sleep Disturbances and Associated Difficulties

Gregory¹,

Parsons²,

Barclay³

et al. 2016

Behavioural Genetics for Education

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Association of polymorphisms in HTR2A, HTR1A and TPH2 genes with suicide attempts in alcohol dependence: A preliminary report

Cited by 38 publications

References 24 publications

Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males

Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males

Genetic studies of alcohol dependence in the context of the addiction cycle

Genetic Research on Sleep, Sleep Disturbances and Associated Difficulties

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