Κατεύθυνση Εφαρμογές της Βιολογίας στην Ιατρική
Library of the School of Science

2023-01-14

2023

Kameta Eleni

Μαρία Γαζούλη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ,
Δημήτριος Στραβοπόδης Αν. Καθηγητής Βιολογίας, ΕΚΠΑ,
Μαρία Ρουμπελάκη Αν. Καθηγήτρια Ιατρικής, ΕΚΠΑ

Μελέτη της γενετικής και επιγενετικής ρύθμισης του αλκοολισμού

English

Study of the genetic and epigenetic regulation of alcoholism

Alcohol use disorders (AUD) are abnormal patterns of heavy alcohol consumption that are related to serious problems. By definition, AUD is considered a combination of alcohol addiction and alcohol abuse. Alcohol abuse is defined as a repetitive high-risk situation of alcohol consumption that causes problems to alcohol addicts and those around them. Alcohol addiction (alcoholism) leads to an out of control addiction with a strong and constant desire for drinking and over time causes dependence and tolerance. Consuming large quantities of alcohol for prolonged periods of time leads to AUD. Alcohol use disorder may cause physical diseases such as pancreatitis, liver disease and a variety of cancers, as well as mental diseases such as dementia and psychiatric disorders. Today the death rate among people with AUD is notably higher compared to the past. Female alcoholics present higher mortality rates than alcohol addicted males. According to research, alcoholism in general is believed to be a complex genetic disease. Variations in numerous genes can increase or decrease a person’s tendency to alcohol. In the global scientific literature there is fundamental evidence for alcoholism that it is a complex multifactorial genetic disease, the involvement of genetic factors in the appearance and development of AUD has been demonstrated while it is now known that variations in many genes can increase or decrease a person’s tendency to alcohol addiction. Disorders resulting from excessive consumption of alcoholic beverages are the result of the cumulative effects caused by extreme alcohol consumption, an individual's genetic profile, environmental factors as well as epigenetic regulation, such as the action of microRNA (miRNA). MiRNA are small (~21-23 nucleotides) non coding RNA (ncRNA) transcripts capable of regulating gene expression at the post-transcriptional level. In 1993 they were first discovered in Caenorhabditis elegans and to date 1,917 miRNA have been identified in humans. MiRNA affect post-transcriptional regulation through mRNA destabilization or degradation, making them ideal regulators of gene expression. Moreover, the silencing induced by miRNA in their target genes is highly specific, allowing physiological responses to be fine-tuned. MiRNA have recently begun to be thoroughly studied and their single nucleotide polymorphisms (SNP) have been found to be associated with a multitude of diseases. MiRNA have now been shown to mediate cellular adaptations induced by exposure to addictive substances such as cocaine, opioids and alcohol. A number of studies have quantified the different expression patterns of miRNA in brains of alcoholics by comparing them with their expression levels in healthy controls. Subsequent studies have focused on determining the expression levels of circulating miRNA in blood and examining whether they can be used as biomarkers in alcohol consumption. The analysis of polymorphisms in the genes encoding microRNA is another interesting approach to the research on the role of microRNA in alcohol consumption. This approach is considered more efficient since the absence or presence of SNP in a miRNA gene does not change whether the DNA is derived from leukocytes or from any other cell type. In the present study we evaluated the associations between the two single nucleotide polymorphisms rs2910164 A>G and rs895819 T>C in the miRNA miR-146a and miR-27a, respectively, and the risk of developing AUD in a group of individuals from the Greek population. Genotypic analysis of miR-146a/rs2910164 A>G and miR-27a/rs895819 T>C polymorphisms was performed in 251 alcoholic patients and 280 healthy controls. Regarding the miR-146a/rs2910164 A>G polymorphism, statistically significant differences were detected in the GC and CC genotypes and in the distribution of the C allele between the group of alcoholic patients and the control group, while it appears that the presence of the GC and CC genotypes as well as the C allele exerts a protective effect against alcoholism disease. Regarding the miR-27a/rs895819 T>C polymorphism, only in the case of the CT genotype were observed highly statistically significant differences between alcoholics and healthy individuals and the C/T genotype seems to act protectively against the appearance and the progression of alcoholism while the homozygous CC genotype appears to be marginally aggravating its role in this disease and the presence of the C allele appears to be unrelated to alcoholism. The results of the present study show that the miR-146a/rs2910164 polymorphism and the CT genotype of the miR-27a/rs895819 polymorphism act protectively against the disease of alcoholism, while the CC genotype of miR27a/rs895819 appears to act marginally aggravatingly against this disease. In the future, it is necessary to carry out further studies on a larger scale and in populations of different nationalities that will examine the relationship of miRNA polymorphisms with AUD. Therefore the results of previous studies will be evaluated and confirmed, new associations will be revealed between miRNA’s SNP and the disorders which are caused by the reckless consumption of alcohol.

Science

Health Sciences

Alcoholism, genetic, epigenetic, SNP, miRNA

Yes

2

Yes

199

76

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https://pergamos.lib.uoa.gr/uoa/dl/object/3257330