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Precision medicine in ovarian carcinoma
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Shailendra Dwivedi, Purvi Purohit, Radhieka Misra, Jeewan Ram Vishnoi, Apul Goel, Puneet Pareek, Sanjay Khattri, Praveen Sharma, Sanjeev Misra, Kamlesh Kumar Pant
Bell et al. (2011) completed a study based on 316 HGS-OvCa samples and compared with normal samples for each individual. The study was based on captured 180,000 exons from 18,500 genes totaling 33 megabases of nonredundant sequence. Enormously parallel sequencing by using the Illumina GAIIx platform or ABI SOLiD 3 platform (80 sample pairs) obtained 14 gigabases per sample bases in total. TP53 was mutated in 303 of 316 samples. BRCA1 and BRCA2 had germ-line mutations in 9% and 8% of cases, respectively, and showed somatic mutations in a further 3% of cases. Further, this group also demonstrated the presence of other mutated genes: RB1, NF1, FAT3, CSMD3, GABRA6, and CDK12.
Genetic influences on antisocial behaviour, problem substance use and schizophrenia: evidence from quantitative genetic and molecular genetic studies
Published in John C. Gunn, Pamela J. Taylor, Forensic Psychiatry, 2014
Pamela J Taylor, Marianne BM van den Bree, Nigel Williams, Terrie E Moffitt
GABA is the primary inhibitory neurotransmitter in the central nervous system. GABAA receptor-mediated chloride currents into neurons are facilitated by a number of drugs, including ethanol, benzodiazepines and barbiturates. GABAA receptor genes α1 (GABRA1, chromosome 5), α2 (GABRA2, chromosome 4), α6 (GABRA6, chromosome 5) , β1 (GABBR1, chromosome 4), β2 (GABBR2, chromosome 9) and γ2 (GABRG2, chromosome 5) have all been associated with sensitivity to alcohol, alcoholism and/or antisocial alcoholism (Kreek et al., 2004; Ducci and Goldman, 2008; Gelernter and Kranzler, 2009; Ho et al., 2010).
Genome-wide association studies of stress score in a Korean Cohort
Published in Stress, 2021
Individual differences in reacting to stress are dependent upon environmental and genetic factors, and genetic variations of candidate genes involved in the regulation of physical stress systems have been studied intensively over the last few decades. For instance, 62% of the etiological variance in glucocorticoid responses can be explained by genetics (Bartels et al., 2003). Further, a T1521C polymorphism in the GABRA6 gene, which belongs to the g-aminobutyric acid (GABA) system responsible for inhibiting the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus-norepinephrine (LC/NE) system, is related to specific personality traits, ANS function (blood pressure), and endocrine effects related to stress (Uhart et al., 2004). More recently, this polymorphism has been linked to the serotonin transporter gene (SLC6A4) (Karg et al., 2011) and the glucocorticoid receptor gene (NR3C1) (Lian et al., 2014). Overall, these studies on genetics have shown that genetic dispositions can influence stress vulnerability and stress-inducing mental disorders (Border et al., 2019).
On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications
Published in Expert Review of Precision Medicine and Drug Development, 2020
Steven J. Nieto, Erica N. Grodin, Lara A. Ray
Alcohol modulates GABA activity directly at receptors and indirectly via stimulation of GABA release. The GABA system contains both ionotropic (GABAA) and metabotropic receptors (GABAB). Pharmacogenetic studies have focused on genes that encode subunits of the GABAA receptor, GABRA6 and GABRG2, as well as a gene that encodes a subunit of the GABAB receptor, GABBR1 (see Table 2). NTX and acamprosate-induced reductions in alcohol craving were dependent on GABRA6 genotype (T + 1519C) [49]. Acamprosate had greater efficacy on cue-induced craving in C homozygotes, while NTX had better efficacy in A carriers. This study also examined an SNP in GABRG2 (G + 3145A) that did not moderate NTX or acamprosate effects on cue-induced craving [49]. Variation in GABBR1 (rs29220) moderates treatment response to baclofen, a selective GABAB receptor agonist. Specifically, C homozygotes with AUD reported greater percentages of days abstinent, less drinking days, and an extended time to relapse compared to G carriers [75]. In sum, genetic variation in GABAergic signaling may be especially relevant to the subjective experience of alcohol [76] and may be useful in predicting treatment response, including clinical response to non-pharmacological treatments, such as Twelve Step Facilitation [77,78].
Evaluation of serum MicroRNA expression profiles in patients with panic disorder
Published in Psychiatry and Clinical Psychopharmacology, 2019
Fikret Poyraz Çökmüş, Erol Özmen, Tunç Alkin, Muhammet Burak Batir, Fethi Sırrı Çam
GABA, the major inhibitory neurotransmitter in the central nervous system, is thought to play an important role in the development of anxiety and panic attacks. A study indicated that stress-associated anxiety and depression suicide risk was elevated in carriers of the GABRA6 rs3219151 T allele [35]. Neurochemical mechanisms that interrupt GABAergic activity can cause anxiety [36,37] and various GABAergic drugs are effective in panic [38,39]. As a result of our study, we determined that miR-1297 and miR-4465 were upregulated in PD group compared with the HCs. These two miRNAs can be expected to regulate gene regions linked to benzodiazepines, which are potent anti-panic drugs. In addition, the gene regions that they affect regulate both benzodiazepine-sensitive GABAA receptors and benzodiazepine-insensitive GABAA receptors. Alcohol, binds to benzodiazepine-insensitive GABAA receptors [40] known to exhibit anxiolytic properties, and the association of alcohol use disorders in patients with PD is common [41,42]. In an alcohol withdrawal study, downregulation of GABRA4 expression is mediated in part by the induction of specific microRNAs [43]. Another study investigating candidate gene regions of PD, 8 of the GABAA receptor subtypes investigated were not associated with PD [44]. Another study found that GABRA5 and GABRB3 were associated with PD [45]. There are more studies investigating the relationship of PD with GABAAA receptor subtypes [46,47]. However, the results are inconsistent and new studies targeting the GABAergic system, GABAA receptor subtypes, and the miRNAs affecting them may be relevant in PD.