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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
Since these publications, these genes and other coding for the α and β subunits of nicotinic acetylcholine receptors, like CHRNA4 and CHRNB3 genes, have been sequenced in tobacco dependence, and some mutations and rare variants have been identified (Thorgeirsson 2010; Olfson 2016; Thorgeirsson 2016). Furthermore, genes have also been investigated in addiction to other substances, including alcohol, opioid and cocaine (Haller 2014). Several GWAS found an association between the initiation of smoking and the functional variant rs6265 of the BDNF gene that encodes the brain-derived neurotrophic factor. These studies also reported an association of the rs3733829 SNP of the CYP2A6 gene (implicated in the metabolism of nicotine into cotinine) and tobacco consumption, but also the development of lung cancer (Thorgeirsson 2010, Tobacco and Genetics Consortium 2010).
Investigation of possible associations of the BDNF, SNAP-25 and SYN III genes with the neurocognitive measures: BDNF and SNAP-25 genes might be involved in attention domain, SYN III gene in executive function
Published in Nordic Journal of Psychiatry, 2022
Hilmi Bolat, Gül Ünsel-Bolat, Semiha Özgül, Erhan Parıltay, Akın Tahıllıoğlu, Luis Augusto Rohde, Haluk Akın, Eyüp Sabri Ercan
We investigated the relationship between polymorphisms of BDNF, SNAP25 and SYN III genes and neuropsychological findings in the cases with inattention symptoms. In our study, BDNF (rs6265), SNAP25 (rs3746544 and rs1051312) and SYN III (rs133946 and rs133945) polymorphisms were associated with variable cognitive measures. BDNF gene (rs6265) polymorphism Met allele carriers and SNAP25 gene (rs3746544) T allele carriers had an association with the attention domain. SNAP25 gene (rs1051312) C allele carriers were only associated with reaction time scores. Cognitive flexibility, which is one of the key components of executive function evaluation, and shifting attention test scores were associated with BDNF (rs6265) Met allele and SYN III (rs133946) gene G allele. SYN III (rs133945) gene C allele carriers had an association with verbal memory correct hit scores.
Machine learning, pharmacogenomics, and clinical psychiatry: predicting antidepressant response in patients with major depressive disorder
Published in Expert Review of Clinical Pharmacology, 2022
William V. Bobo, Bailey Van Ommeren, Arjun P. Athreya
Kautzky and colleagues similarly leveraged clustering and RFs to predict response after 4 weeks of treatment with antidepressants or electroconvulsive therapy (ECT) using 12 SNPs in or near HTR2A (rs643627, rs6313), COMT (rs4680), ST8SIA2 (rs8035760, rs3784723), PPP3CC (rs7430, rs10108011), and BDNF (rs6265, rs11030101, rs11030104, and rs12273363) in 225 depressed participants in the Group for the Study of Resistant Depression (GSRD) cohort [59,60]. MDD diagnoses were confirmed using a modified version of the Mini-International Neuropsychiatric Interview (MINI), version 5.0.0 [61]. SNPs were selected based on literature review. Study drugs included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NARIs), tricyclic and tetracyclic antidepressants, and monoamine reuptake inhibitors (MAOIs). There was no stratification based on antidepressants or intervention types. Response to treatment was defined as achieving a HAMD score ≤17 after one or two adequate trials of antidepressants. The RF model was trained using 10-fold cross-validation, and the trained models were not validated in an external dataset. A four-factor RF model incorporating three SNPs (rs6265, rs6313, and rs7430) and melancholic depressive subtype was associated with a 4-fold higher chance of positive treatment response compared with other patients (OR 4.22, 95% CI 1.43–12.49).
The BDNF rs6265 variant may interact with overweight and obesity to influence obesity-related physical, metabolic and behavioural traits in Pakistani individuals
Published in Annals of Human Biology, 2018
Sobia Rana, Saad Mirza, Soma Rahmani
As BDNF plays a key role in the leptin proopiomelanocortin pathway that regulates body weight and overall metabolic fitness, polymorphisms of the BDNF gene might affect energy balance and may lead to manifestation of obese phenotype. One important polymorphism, rs6265, present in the coding region of the BDNF gene involves a G>A transition at the 196th nucleotide position that in turn results in valine to methionine substitution at the 66th amino acid position (Val66Met) of the N-terminal domain of pro-BDNF. Mechanistically, the amino acid change does not alter the mature BDNF protein, rather it appears to impair intracellular trafficking and depolarisation-induced release of BDNF without changing its baseline constitutive secretion (Egan et al. 2003; Chen et al. 2004).