title: Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 variations does not impact alcohol dependence disorder features.
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 < or = 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.
authors.affiliation: Institute of Psychiatry, University of Bologna, Italy. antonio.drago@unibo.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Drago
authors.forename: Ioannis
authors.initials: I
authors.lastname: Liappas
authors.forename: Carmine
authors.initials: C
authors.lastname: Petio
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Petros
authors.initials: P
authors.lastname: Malitas
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Antonis
authors.initials: A
authors.lastname: Politis
authors.forename: Elias O
authors.initials: EO
authors.lastname: Tzavellas
authors.forename: Katerina K
authors.initials: KK
authors.lastname: Zisaki
authors.forename: Francesca
authors.initials: F
authors.lastname: Prato
authors.forename: Sara
authors.initials: S
authors.lastname: Batelli
authors.forename: Letizia
authors.initials: L
authors.lastname: Polito
authors.forename: Diana
authors.initials: D
authors.lastname: De Ronchi
authors.forename: Thomas
authors.initials: T
authors.lastname: Paparrigopoulos
authors.forename: Anastasios
authors.initials: A
authors.lastname: Kalofoutis
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D014644:Genetic Variation; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D011594:Psychometrics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C508584:IL1A protein, human; C508585:IL1B protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014409:Tumor Necrosis Factor-alpha; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase