We recently showed that a trinucleotide polymorphism within the coding region of the androgen receptor (AR) is linked to craving in alcohol withdrawal, an effect that was mostly mediated by leptin.
The objective of our study was to investigate the dynamics of leptin gene promoter methylation during alcohol withdrawal and specific treatment in a rodent (rat) model for alcohol dependence.
Our results show on the one hand negative associations between the number of CAG repeats and (i) leptin serum levels (P<0.01) and (ii) craving (P<0.05), and on the other hand, a positive association between leptin and craving of man in alcohol withdrawal (P<0.001).
In this study, we examined the genetic variant -45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction-based single-strand conformational polymorphism analysis.
To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon-intron boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS.
The role of SorCS2 in the acute and adapted response to alcohol was therefore investigated by comparing SorCS2 knockout (<i>Sorcs2<sup>-/-</sup></i> ) mice to wild type (WT) mice in three paradigms modeling alcohol sensitivity and consumption; alcohol-induced conditioned place preference, two-bottle choice test as well as the behavioral response to alcohol withdrawal.
The top association signal for AW severity was in sortilin family neurotrophin receptor gene SORCS2 on chromosome 4 (European American meta-analysis n = 1,478, p = 4.3 × 10<sup>-9</sup> ).
In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal.
Based on our data, the impact of the 9-repeat allele of the dopamine transporter gene in alcoholism and the severity of alcohol withdrawal symptoms is putatively not substantial.