Preclinical studies implicate the gene encoding the alpha synuclein protein (SNCA) in the pathophysiology of alcohol dependence and dopamine neuron function.
We observed a significant increase of the alpha synuclein promoter DNA methylation in patients with alcoholism which was significantly associated with their elevated homocysteine levels.
The GABA(B) receptor agonist, baclofen, has shown promising effects in patients suffering from pain, post-traumatic stress disorder, alcoholism, overactive bladder and gastroesophageal reflux disease.
The analysis revealed a candidate SNP from CHRNA5, rs16969968, associated with both ND and AD, and replicated the findings in an independent dataset with a P-value of 1.06 × 10(-03) .
Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease.
Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools.
Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.
As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.
These data also suggest that positive allosteric modulation of the GABA(B) receptor may constitute a potential strategy for developing new drugs for treating alcohol dependence.
Our findings suggest that the investigated GABABR1 variants do not contribute a substantial effect (RR > 3) to the genetic variance of alcohol dependence.
After binding to the neurokinin-1 (NK-1) receptor, SP regulates many pathophysiological functions in the central nervous system, such as emotional behavior, stress, depression, anxiety, emesis, vomiting, migraine, alcohol addiction, seizures and neurodegeneration.
Genetic deletion or antagonism of the neurokinin 1 receptor (NK1R) decreases alcohol intake, alcohol reward, and stress-induced alcohol relapse in rodents, while TACR1 variation is associated with alcoholism in humans.
Each of the 5 SNPs in the TACR1 gene that was significantly related to AD severity in the SAGE data set and/or the BOLD response to the craving task is near the 3' or 5' areas of the gene and may therefore be near mutations with potential functional significance.
Four single-nucleotide polymorphisms (rs3771829, rs3771833, rs3771856, and rs1701137) at the TACR1 gene, previously known to be associated with bipolar disorder or alcoholism, were strongly associated with ADHD.
We develop a pharmacokinetic model describing how genetic variations in ADH1B, ADH1C, ADH7, ALDH2, and TAS2R38 affect consumption behavior, and alcohol and acetaldehyde levels over time in various tissues of individuals with a particular genotype to predict their susceptibility to alcohol dependence.
We used family-based association methods to test for association between TAS2R38 haplotypes and alcohol dependence as well as a measure of alcohol consumption (Maxdrinks) and age of onset of drinking behaviors in a sample of families densely affected with alcoholism.
These results are inconsistent with the view that excessive use of alcohol causes the association between nontasting and alcoholism and are consistent with the view that there is a genetic association between PROP/PTC-tasting and alcoholism.
Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required.