Genetics of Lesch's typology of alcoholism
It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.
Available from: Samuel Pombo
- "orring et al . 1987 ; Cloninger et al . 1996 ) , neuro - chemical parameters ( von Knorring et al . 1985 ; Tupala et al . 2003 ; Bleich et al . 2004 ) , craving ( Hillemacher et al . 2006a , 2006b ) , cognitive functioning ( Zago - Gomes and Nakamura - Palacios 2009 ) , and genetic polymorphisms ( Tiihonen et al . 1999 ; Hallikainen et al . 2000 ; Samochowiec et al . 2008 ) . While classifi cation schemes used to identify subtypes can be fairly established , additional studies to explore their clinical implications are needed . Th erefore , we also exam - ined if ATs signifi cantly infl uence the clinical management of alcohol dependence . A lower healthcare resource use and a higher rate of relapse were"
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The current nosological classifications may describe a syndrome of "alcoholism" that is too heterogeneous to produce prognostic models for clinical management. Multidimensional alcoholism typologies (ATs) could represent a valuable paradigm in the search for targeted treatment. The main goal of this study was to evaluate the clinical implications of 3 empirically-validated ATs, focusing on various measures of clinical performance.
This was a 3-month naturalistic study in which drinking status, and participation in the clinical protocol and group psychotherapy were recorded and used as indicators of treatment performance. The clinical profiles of the subtypes were also compared and graphically presented. Alcohol-dependent outpatients were classified according to the Cloninger, Lesch, and NETER typologies.
The results showed that the type II (Cloninger), type IV (Lesch), and sociopathic and addictopathic (NETER) subgroups showed a worse outcome in terms of abstinence rates and clinical healthcare resource use.
Our findings point to the need to differentiate multidimensional alcoholism subtypes before planning the clinical management of alcohol use disorders.
Available from: PubMed Central
- "Our previous study focused on genetic variants of the dopamine transporter DAT, D2 receptor (DRD2), serotonin transporter (5HTT), and catechol-O-methyltransferase (COMT) in different subgroups of Lesch's typology. We have found no evidence for the role of these gene polymorphisms in Lesch type 1 and 2 subjects . "
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ABSTRACT: Lesch's typology differentiates alcoholics into different treatment response subgroups. The effects of ethanol are mediated, to an important extent, via the GABA-ergic system.
We have evaluated the linkage disequilibrium patterns and haplotype frequencies of GABRG1 and GABRA2 genes in 133 alcoholics divided according to Lesch's typology and in 145 matched controls.
Besides several relationships at a threshold of statistical significance, we found no significant differences in the haplotype distribution of these genes between alcoholics and controls.
Lesch's typology may not be related with the genotype of alcoholics - at least in terms of genes with an established role in the development of dependency.
Available from: Paul Corcoran
- "Most studies looking at an association between SCL6A4 and alcohol dependence have focused on the 5-HTTLPR polymorphism, with inconclusive results. Several case-control association studies support our negative findings (Gorwood et al., 2000; Thompson et al., 2000; Kranzler et al., 2002; Foley et al., 2004; Choi et al., 2006; Köhnke et al., 2006; Dick et al., 2007; Mokrović et al., 2008; Samochowiec et al., 2008). However, higher frequencies of the S/S genotype (Sander et al., 1997), or the S allele (Konishi et al., 2004a,b) in alcohol dependent patients have been reported and these results are supported by case-control based meta-analytic evidences showing that the S allele could be a risk factor for a phenotype related to alcohol dependence (Gorwood et al., 2004; Feinn et al., 2005), specially among alcohol dependent patients with psychiatry comorbidity , early-onset, or greater severity (Feinn et al., 2005). "
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ABSTRACT: Twin studies suggest that genetic factors account for 40-60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence.
165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.
Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of -1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI)=1.98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df)=10.21 (4), p=0.037). The association of -1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups.
Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.
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