title: Interleukin-6 promoter polymorphism interacts with pain and life stress influencing depression phenotypes.
abstract: Interleukin-6 (IL-6) has emerged as a potent biomarker for depression as its elevated plasma levels in patients with clinical depression have been confirmed by meta-analyses. Increased plasma IL-6 concentration was associated with various psychological stress factors and physical disorders accompanied by pain. Another modulator of the IL-6 level is rs1800795, a promoter polymorphism in the IL-6 gene which is able to influence its expression rate. Therefore, we examined in a Hungarian population sample of 1053 volunteers with European origins if rs1800795 polymorphism can affect depression symptoms measured by Zung Self-rating Depression Scale (ZSDS), and Brief Symptom Inventory (BSI). We also investigated the interactions of the polymorphism with reported painful physical conditions and Recent Negative Life Events (RLE) measured by the List of Life Threatening Experiences. Rs1800795 significantly interacted with both RLE and painful condition on depressive symptoms measured by ZSDS and BSI using different heritability models, while no main effects of the polymorphism were identified. After correction for multiple testing only the rs1800795 × RLE interaction effect (recessive model) remained significant on the BSI score, while both RLE and painful conditions significantly interacted on the ZSDS. In conclusion, the functional IL-6 rs1800795 polymorphism in interaction with various stress factors increases the risk of depression and has a greater impact on symptoms measured by the ZSDS. Thus, IL-6 and other cytokines may be more relevant in the development of somatic symptoms compared to affective signs of depression, delineating a specific genotype-phenotype relationship in this heterogeneous disorder.
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary. thadeous.smith@gmail.com.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary. thadeous.smith@gmail.com.
authors.forename: David
authors.identifier: 0000-0003-3867-5065
authors.initials: D
authors.lastname: Kovacs
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary.
authors.forename: Nora
authors.initials: N
authors.lastname: Eszlari
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Petschner
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Pap
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Vas
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|National Institute of Oncology, Rath Gyorgy u. 7-9, Budapest, Hungary.|School of Mental Health Sciences, Semmelweis University, Balassa u. 6, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary.|Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Kútvölgyi u.4, Budapest, Hungary.
authors.forename: Xenia
authors.initials: X
authors.lastname: Gonda
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bagdy
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4., Budapest, 1089, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4., Budapest, Hungary.|Neuroscience and Psychiatry Unit, University Manchester, Manchester, M13 9PT, UK.|MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyvarad ter 4., Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Juhasz
mesh_terms: D000293:Adolescent; D000328:Adult; D003866:Depressive Disorder / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics*; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Depression; Interleukin-6; Pain; Polymorphism; Stress; Zung Self-rating Scale
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