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Abstract
Background: Major depressive disorder is a condition associated with dysregulated cytokine levels; among these, IL6. Furthermore, genetic variations within cytokine genes have been proposed to predict antidepressant treatment outcome.
Objectives: This study aims to evaluate the role of IL6-174G > C and IL6R D358A A > C functional polymorphisms in antidepressant treatment phenotypes, specifically remission, relapse, and treatment resistant depression (TRD).
Methods: The referred polymorphisms were genotyped in 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months.
Results: It was found that patients carrying IL6-174 GC genotype present a protection towards the development of TRD (OR = 0.242; 95% CI = 0.068–0.869; p = .038), when compared with GG genotype. Additionally, carriers of IL6-174 CC genotype remit earlier than patients with IL6-174 GG/GC genotypes, with a median time to remission of 6 weeks for CC carriers and 15 weeks for GG or GC carriers (p = .030, Log-rank test). No association was found between IL6R D358A genetic polymorphism and any of the treatment phenotypes evaluated.
Conclusions: The IL6-174G > C polymorphism influences antidepressant treatment outcome in this sub-set of MDD patients, providing a putative mechanistic link for the dysregulated IL-6 levels described in the literature in patients with TRD.
Acknowledgements
The authors would like to thank the contribution of Ma Céu Lamas (Hospital Magalhães Lemos) on the blood sample collection, and the Genomics unit of IGC for the genotyping services.
Disclosure statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Funding
Funding for this study was partially provided by AstraZeneca Foundation; the AstraZeneca Foundation had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. MS holds a grant from Instituto Politécnico do Porto (IPP/P-067/2015).