title: The role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes: A preliminary report.
abstract: Recent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n=3 and n=5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C>A and IL18-137G>C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression.
authors.affiliation: Molecular Oncology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, Porto, Portugal; Núcleo de Investigação e Informação em Farmácia-Centro de Investigação em Saúde e Ambiente (CISA), School of Allied Health Technologies, Polytechnic Institute of Porto, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: mmarlenes@gmail.com.
authors.forename: Marlene
authors.initials: M
authors.lastname: Santos
authors.affiliation: Hospital de Magalhães Lemos, Porto, Portugal; Instituto Superior de Ciências da Saúde, Norte, Portugal.
authors.forename: Serafim
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Núcleo de Investigação e Informação em Farmácia-Centro de Investigação em Saúde e Ambiente (CISA), School of Allied Health Technologies, Polytechnic Institute of Porto, Porto, Portugal; Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Lima
authors.affiliation: Clínica Médico-Psiquiátrica da Ordem, Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Mota-Pereira
authors.affiliation: Trás-os-Montes e Alto Douro Hospital Centre, Vila Real, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Pimentel
authors.affiliation: Trás-os-Montes e Alto Douro Hospital Centre, Vila Real, Portugal.
authors.forename: Dulce
authors.initials: D
authors.lastname: Maia
authors.affiliation: Hospital de Magalhães Lemos, Porto, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Correia
authors.affiliation: Hospital de Magalhães Lemos, Porto, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Gomes
authors.affiliation: Núcleo de Investigação e Informação em Farmácia-Centro de Investigação em Saúde e Ambiente (CISA), School of Allied Health Technologies, Polytechnic Institute of Porto, Porto, Portugal.
authors.forename: Agostinho
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Molecular Oncology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, Porto, Portugal; Department of Pathology and Molecular Immunology, ICBAS, Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal; Health Faculty of University Fernando Pessoa, CEBIMED, Porto, Portugal; Research Department, Portuguese League Against Cancer (Norte), Porto, Portugal. Electronic address: ruimedei@ipoporto.min-saude.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D020382:Interleukin-18; D012333:RNA, Messenger
keywords: Antidepressants; Cytokines; Genetic polymorphisms; IL18; Relapse