An exploratory study of candidate gene(s) for Delirium Tremens: Adding the new cholinergic dimension to the conundrum.

BACKGROUND AND AIMS: Delirium Tremens (DT) is the most severe form of alcohol withdrawal syndrome, with a potential risk of mortality. Search for the predictors of DT led to study of candidate genes, with inconsistent and inconclusive results. This study aimed to explore the association of various candidate gene polymorphisms and DT in a case-control design. METHODS: This was a genetic association study with a case control design. Two hundred ten Alcohol dependent (AD) male subjects and 200 age matched controls were recruited. DT was diagnosed with the help of Semi-structured Assessment for Genetics of Alcoholism. SNP genotyping was done using TaqMan assay by real time PCR (q-PCR). RESULTS: T allele carrying status (GT and TT) [rs1824024] of muscarinic cholinergic receptor 2 (CHRM2) was found to be significantly associated with DT. When compared to the general population, this genetic polymorphism was not found to be more common in alcohol dependence per se, which excludes the possibility of spurious association between CHRM2 and DT. Withdrawal seizure was more common in the DT group and came out to be one of the important predictors of DT. However, the genetic association was found to be specific for DT, not related to withdrawal seizures. CONCLUSION: The present research added a new cholinergic dimension in the genetic association and biological mechanism of DT.

Subtyping of alcohol dependence in Indian males: A cluster analytic approach.

OBJECTIVES: Two cluster solutions for the subtyping of alcohol dependence (AD) was investigated in an Indian male population. Subtypes were compared for various personality traits and childhood externalizing disorders. They were also compared with respect to single-nucleotide polymorphisms (SNP) of various candidate genes. MATERIALS AND METHODS: This was a clinic-based study conducted among 202 patients with AD. All patients were assessed with SSAGA-II for comorbid antisocial personality disorder (ASPD) and childhood conduct disorder (CD), oppositional defiant disorder (ODD), and attention deficit hyperactivity disorder (ADHD). For the assessment of personality traits, the Indian Adaptation of Sensation Seeking Scale (SSS) and Barratt's Impulsiveness Scale were administered. SNP genotyping was done using taqmann assay by real-time polymerase chain reaction. RESULTS: Among those with AD, the two-cluster model which was able to produce the maximum degree of cohesion among disorders in the same cluster and separateness from the other cluster was the one with or without ASPD and CD. The quality of the cluster analysis was reduced when ODD and ADHD were included in the model along with ASPD and CD. Thus, in our index population, there are two distinct clusters of AD, one with ASPD and CD or the externalizing cluster (Cluster 2) and the other without ASPD and CD or the nonexternalizing cluster (Cluster 1). Externalizing cluster had significantly higher score in both the impulsiveness and the SSS. This cluster was also significantly associated with childhood ADHD and ODD. The genotype frequencies of all candidate genes were found to be nonsignificantly distributed among the two groups. CONCLUSION: Our study has conferred a cross-cultural validation of the known alcoholism subtypes.