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.
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).
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.
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.
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.
Our findings suggest that the CAT c.-262C>T genetic polymorphism influences the susceptibility to alcohol dependence and severity of alcohol dependence, while CYP2E1 c.-1053C>T polymorphism influences the expression of obsessive-compulsive and anxiety symptoms.
In a nutshell, transition of a single nucleotide may modify differential DNA-protein interactions at OPRK1 and PDYN׳s SNPs, significantly associated with pathology that may lead to altered individual vulnerability for alcohol dependence.
Simultaneous genotyping of single-nucleotide polymorphisms in alcoholism-related genes using duplex and triplex allele-specific PCR with two-step thermal cycles.
The association between the OPRM1 A118G (Asn40Asp, rs1799971) polymorphism and alcohol use disorders and alcohol consumption was analyzed using three different population-based samples: (a) a Finnish cohort study, Health 2000, with 503 participants having a DSM-IV diagnosis for alcohol dependence and/or alcohol abuse and 506 age- and sex-matched controls; (b) a Finnish cohort study, FINRISK (n = 2360) and (c) the Helsinki Birth Cohort Study (n = 1384).
Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5' and 3' functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs/ondansetron respectively.
We investigated whether variation in genes encoding cytochrome P450 2E1 (CYP2E1) or acetaldehyde-metabolising enzymes (ALDH1A1, ALDH2) might alter the risk of AD, with and without symptoms of anxiety, in a Cape population with mixed ancestry.
Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5' and 3' functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs/ondansetron respectively.
First, with the Principle Component analysis, six proteins, CYP2E1, FAM25, CA3, BHMT, HIBADH and ECHS1, involved in oxidation reduction, energy and lipid metabolism and amino acid metabolism, were identified as the most differentially expressed gene products across all of the experimental conditions of our chronic alcoholism model.
We previously reported moderating effects of age of onset of alcohol dependence (AD) and a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter protein in a sample of 134 individuals participating in a 12-week, placebo-controlled trial of sertraline.
Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.
Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another.
Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.