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Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features
Institute of Psychiatry, University of Bologna, Italy
Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece
Neuroscience Department. Istituto di ricerche Farmacologiche \"Mario Negri\", Milan, Italy
European Centre for the Quality of Life – E.C.Qua.L., Athens, Greece
Laboratory of Biological Chemistry University of Athens Medical School, Greece
Division of Geriatric Psychiatry Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece
Department of Pharmacology, University of Athens Medical School, Athens, Greece
Biomedical Research Foundation of Academy of Athens, Greece
Department of Mental Health, Azienda USL di Bologna, Bologna, Italy
* Author to whom correspondence should be addressed.
Received: 30 June 2009 / Accepted: 13 July 2009 / Published: 16 July 2009
Abstract: We assessed a set of biological (HDL, LDL, SGOT,SGPT, GGT, HTc, Hb and T levels) and psychometric variables (investigated through HAM-D, HAM-A, GAS, Liebowitz Social Anxiety Scale, Mark & Mathews Scale, Leyton scale, and Pilowski scale) in a sample of 64 alcohol dependent patients, at baseline and after a detoxification treatment. Moreover, we recruited 47 non-consanguineous relatives who did not suffer alcohol related disorders and underwent the same tests. In both groups we genotyped 11 genetic variations (rs1800587; rs3087258; rs1799724; 5-HTTLPR; rs1386493; rs1386494; rs1487275; rs1843809; rs4570625; rs2129575; rs6313) located in genes whose impact on alcohol related behaviors and disorders has been hypothesized (IL1A, IL1B, TNF, 5-HTTLPR, TPH2 and HTR2A). We analyzed the epistasis of these genetic variations upon the biological and psychological dimensions in the cases and their relatives. Further on, we analyzed the effects of the combined genetic variations on the short – term detoxification treatment efficacy. Finally, being the only not yet investigated variation within this sample, we analyzed the impact of the rs6313 alone on baseline assessment and treatment efficacy. We detected the following results: the couple rs6313 + rs2129575 affected the Leyton -Trait at admission (p = 0.01) (obsessive-compulsive trait), whilst rs1800587 + 5-HTTLPR impacted the Pilowski test at admission (p = 0.01) (hypochondriac symptoms). These results did not survive Bonferroni correction (p ≤ 0.004). This lack of association may depend on the incomplete gene coverage or on the small sample size which limited the power of the study. On the other hand, it may reflect a substantial absence of relevance of the genotype variants toward the alcohol related investigated dimensions. Nonetheless, the marginal significance we detected could witness an informative correlation worth investigating in larger samples.
Keywords: gene; alcohol dependence; IL1A; IL1B; TNF; 5HTPR; HTR2A; TPH2; association
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Drago, A.; Liappas, I.; Petio, C.; Albani, D.; Forloni, G.; Malitas, P.; Piperi, C.; Politis, A.; Tzavellas, E.O.; Zisaki, K.K.; Prato, F.; Batelli, S.; Polito, L.; De Ronchi, D.; Paparrigopoulos, T.; Kalofoutis, A.; Serretti, A. Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features. Int. J. Environ. Res. Public Health 2009, 6, 1980-1990.
Drago A, Liappas I, Petio C, Albani D, Forloni G, Malitas P, Piperi C, Politis A, Tzavellas EO, Zisaki KK, Prato F, Batelli S, Polito L, De Ronchi D, Paparrigopoulos T, Kalofoutis A, Serretti A. Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features. International Journal of Environmental Research and Public Health. 2009; 6(7):1980-1990.
Drago, Antonio; Liappas, Ioannis; Petio, Carmine; Albani, Diego; Forloni, Gianluigi; Malitas, Petros; Piperi, Christina; Politis, Antonis; Tzavellas, Elias O.; Zisaki, Katerina K.; Prato, Francesca; Batelli, Sara; Polito, Letizia; De Ronchi, Diana; Paparrigopoulos, Thomas; Kalofoutis, Anastasios; Serretti, Alessandro. 2009. "Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features." Int. J. Environ. Res. Public Health 6, no. 7: 1980-1990.