To date, the only genes that have been consistently replicated across racial and ethnic groups to influence alcoholism vulnerability are polymorphisms in the alcohol-metabolizing enzymes, i.e. cytosolic alcohol dehydrogenase 1B (ADH1B) and mitochondrial aldehyde dehydrogenase 2 (ALDH2).
In this study the functional effects of the two SNPs (rs1159918 and rs1229982) in the proximal promoter region of ADH1B that were associated with alcoholism were explored.
The hypothesized mechanism underlying the associations of the ADH1B and ALDH2 polymorphisms with alcohol dependence is that the isoenzymes encoded by these alleles lead to an accumulation of acetaldehyde during alcohol metabolism.
Studies of the ADHIBand ADH1C haplotypes, however, have shown that ADH1C*I is in linkage disequilibrium with ADHiB*2, and the ADH1C*i allele does not appear to have significant unique associations with alcohol dependence.
Direct correlations of blood ethanol and acetaldehyde concentrations, cardiovascular haemodynamic responses, and the subjective perceptions after challenge with low (0.2g/kg) to moderate (0.5g/kg) alcohol in individuals with different ALDH2 genotypes support the notion that full protection against alcoholism byALDH2*2/*2 may derive from either abstinence or deliberate moderation in alcohol consumption due to strong discomfort from physiological and psychological responses caused by persistently elevated blood acetaldehyde after ingestion of a small amount of alcohol, and that the partial protection by ALDH2*1/*2 can be ascribed to significantly lower acetaldehyde build-up in blood and the according adverse reactions.
Data are consistent with the hypothesis that elevations in acetaldehyde, increased sensitivity to alcohol, and lower levels of drinking reflect the mechanism by which the ALDH2*2 allele reduces risk for alcohol dependence.
Polymorphism in the serotonin transporter gene and moderators of prolactin response to meta-chlorophenylpiperazine in African-American cocaine abusers and controls.
Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.
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 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.
Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria.
The role of cholecystokinin (CCK), CCK-A or CCK-B receptor antagonists in the spontaneous preference for drugs of abuse (alcohol or cocaine) in naive rats.
SNPs in NPY2R provided significant evidence of association with alcohol dependence, alcohol withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence (all p < 0.03).