Association of FKBP5, COMT and CHRNA5 polymorphisms with PTSD among outpatients at risk for PTSD
| Autor: | Stuart N. Hoffman, Joseph A. Boscarino, Margaret Rukstalis, Walter F. Stewart, Porat M. Erlich |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Genotype Genome-wide association study Single-nucleotide polymorphism Nerve Tissue Proteins Receptors Nicotinic Catechol O-Methyltransferase behavioral disciplines and activities Article Stress Disorders Post-Traumatic Tacrolimus Binding Proteins Risk Factors Internal medicine mental disorders Outpatients medicine Humans Genetic Predisposition to Disease Psychiatry Biological Psychiatry Aged Polymorphism Genetic biology CHRNA5 Middle Aged Neuroticism Eastern european Psychiatry and Mental health biology.protein Anxiety Female FKBP5 medicine.symptom Psychology rs4680 Genome-Wide Association Study |
| Popis: | To the Editor: Several genetic components for posttraumatic stress disorder (PTSD) have been identified, including biologic pathways involving the hypothalamic–pituitary–adrenocortical, locus coeruleus/noradrenergic, and the limbic systems (Broekman, et al., 2007; Koenen, 2007; Rauch and Drevets, 2009). In our IRB-approved study, lifetime PTSD was assessed among adult outpatients with chronic, non-malignant pain, a condition commonly associated with PTSD (McFarlane, 2010). We assessed PTSD with an instrument widely used in previous epidemiologic studies (Boscarino et al., 2010). We examined genetic markers using a multivariate design that assessed single nucleotide polymorphisms (SNPs) located within the FK506 binding protein-5 (FKBP5), catechol-O-methyltransferase (COMT), and cholinergic receptor nicotinic alpha3/alpha-5 (CHRNA3/CHRNA5) gene clusters. SNPs were selected using agnostic LD tagging with consideration of prior evidence and functional annotation (Erlich, et al., 2010). The COMT gene is associated with anxiety disorders, psychosis, depression, and other conditions involving catecholamine pathway regulation (Craddock, et al., 2006; Montag et al., 2008). This gene is also associated with PTSD (Kolassa et al., 2010). The FKBP5 gene regulates glucocorticoid receptor sensitivity, is functionally involved in HPA stress axis activity, and is associated with PTSD (Binder, 2009; Gillespie, et al., 2009). The CHRNA3/5 gene cluster, which encodes components of the nicotinic acetylcholine receptor, is associated with nicotine dependence, smoking, and other substance misuse (Erlich, et al., 2010). PTSD is also associated with cigarette smoking and substance use (Boscarino et al., 2006; Fu et al., 2007). Using trained interviewers and following informed consent, we completed diagnostic interviews with 502 subjects and collected DNA to determine if FKBP5, COMT, and CHRNA3/5 SNPs were associated with PTSD (mean age = 55, S.D. = 13.4; PTSD = 15%, 95% CI = 11.7–18.1%). Non-Caucasian patients were excluded from this analysis. Genotyping was performed on an Applied BioSystems 7500 real-time PCR platform, using TaqMan kits. Using multivariate logistic regressions that included demographic (age, gender, income, education, and marital status) and environmental (trauma exposure, childhood adversity, and neuroticism) variables, 3 of 9 SNPs examined were associated with PTSD (p |
| Databáze: | OpenAIRE |
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