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A Genetic Framework for Addiction
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Philip Gorwood, Yann Le Strat, Nicolas Ramoz
Catechol-O-methyltransferase (COMT) metabolizes dopamine. The human COMT gene contains a functional polymorphism (Val158Met, SNP rs4680), with individuals carrying the Val allele having a 40% higher enzyme activity than Met homozygotes, at least in the frontal cortex. The COMT Val158Met variant represents a good candidate for association with addiction (Tunbridge 2012). Studies between COMT and drug-addiction-related phenotypes have showed inconsistent results, meta-analyses considering alcohol or illicit drugs being negative. However, these studies were conducted in relatively small samples, with a high heterogeneity.
Evaluation of COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in synthetic cannabinoid use disorder patients
Published in Journal of Addictive Diseases, 2020
Sacide Pehlivan, Hasan Mervan Aytac, Selin Kurnaz, Mustafa Pehlivan, Pinar Cetinay Aydin
Catechol-O-methyltransferase (COMT) is an enzyme found in the central nervous system that inactivates dopamine, epinephrine, and norepinephrine. A variation in the COMT gene exchanging valine to the methionine amino acid at position 108/158 results in two common enzyme variants: Val and Met. While the Met allele of COMT is associated with low enzymatic activity, the Val allele is associated with increased enzymatic activity.5 COMT (rs4680) variants may affect COMT activity in the brain, altering dopamine neurotransmission known to play a prominent role in reward and addiction.6 Cannabinoid receptors that bind to both exogenous and endogenous cannabinoids are seven-transmembrane domain G-protein-coupled receptors. The cannabinoid receptor-1 (CB1) is encoded by the cannabinoid receptor type 1 (CNR1) gene, while the cannabinoid receptor-2 (CB2) is encoded by the cannabinoid receptor type 2 gene (CNR2), which has been actively investigated for its role in osteoporosis, inflammation, leukemia, several types of cancer, and addiction.7
Genetic risk factors for cancer-related cognitive impairment: a systematic review
Published in Acta Oncologica, 2019
Cecilie D. R. Buskbjerg, Ali Amidi, Ditte Demontis, Eva R. Nissen, Robert Zachariae
Two cross-sectional studies found COMT variants to be significantly associated with CRCI in BC patients following CT [24,29]. In one study, COMT Val carriers (rs4680) had poorer performance on tests of motor speed, attention, and verbal fluency compared with COMT Met carriers, with effect sizes ranging from OR = 1.73 (95% CI: 1.17–2.57) to 1.87 (95% CI: 1.26–2.78) (Table 1). In addition, COMT Val was shown to interact with CT to induce poorer performance in attention tests in CT-treated COMT Val carriers compared with non-treated COMT Val carriers (OR = 5.63, 95% CI: 1.95–16.28) [29]. In contrast, no association between the rs4680 and cognitive functioning was found in the second study. This study, however, reported statistically significant associations between cognitive functioning and another COMT SNP (rs165599), with homozygous G individuals being at increased risk for cognitive decline compared with heterozygous and homozygous A individuals [24]. Importantly though, these latter results did not appear to have been corrected for multiple testing. One cross-sectional [25] and one longitudinal [14] study investigated a variant (rs6265) in BDNF, but found no statistically significant associations of rs6265 with post-CT cognitive impairments in BC patients.
Association of COMT gene variability with pain intensity in patients after total hip replacement
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2019
Anna Machoy-Mokrzyńska, Zuzanna Starzyńska-Sadura, Violetta Dziedziejko, Krzysztof Safranow, Mateusz Kurzawski, Katarzyna Leźnicka, Violetta Sulżyc-Bielicka, Alina Jurewicz, Andrzej Bohatyrewicz, Monika Białecka
Catechol-O-methyltransferase metabolises dopamine, adrenaline and noradrenaline, and is a key modulator of dopaminergic and adrenergic neurotransmission. There are two major forms of the COMT enzyme that differ by 50 amino acids at the N terminus, namely membrane-bound COMT (MB-COMT) and soluble COMT (S-COMT). The rs6269 SNP is located in the promoter region of S-COMT [6]. Three other SNPs (rs4633, rs4818 and rs4680) are situated within the coding region for both S- and MB-COMT (the National Center for Biotechnology Information genome database; www.ncbi.nlm.nih). Variations in SNPs rs4633 and rs4818 are synonymous, whereas variation in SNP rs4680 is nonsynonymous and codes for the substitution of valine (Val) by methionine (Met) at codon 158 for MB-COMT and at codon 108 for S-COMT. This scenario produces an enzyme with a lower thermostability, which results in decreased enzyme activity under physiological conditions [7].