title: A Study on the Association of Interleukin-1 Cluster with Genetic Risk in Bipolar I Disorder in Iranian Patients: A Case-control Study.
abstract: The pathogenesis of Bipolar I Disorder (BP-I) involves immune-mediated mechanisms, especially an imbalance in pro-inflammatory/anti-inflammatory cytokines in plasma or cerebrospinal fluid. Interleukin-1 (IL-1) gene cluster, coding some of these pro-inflammatory cytokines, might play a role in various neuropathologies related to neuron inflammation. The aim of the present study was to investigate the possible role of IL-1 gene cluster polymorphisms in determining the susceptibility to BP-I in Iranian population. 48 patients with BP-I in Mashhad (in north-eastern Iran), diagnosed by two psychiatrists using SCID (structured clinical interview for DSM disorders) were selected through convenient sampling and were compared with 47 healthy controls, voluntarily enrolled in the study. Patients with non-Persian ethnicity, history of immunoallergic disorders, endocrinopathies, neurologic disorders, and substance-induced mood disorders were excluded from both case and control groups. Genotyping of IL-1 gene cluster polymorphisms, including IL-1a-889, IL-1b +3954, IL-1b-511, and IL-1RN (VNTR) were carried out using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and compared by SPSS using Fisher's exact and chi-square tests. The frequency of IL-1b-511 CC genotype and C/T allelic frequency were significantly different between BMD patients and healthy controls (p=0.04 and p=0.02, respectively). Among patients, -511 T allele was significantly more frequent in those with a positive history of major depression. Moreover, +3954 T allele was significantly more frequent in early onset BMD patients. The results suggest a positive association between IL-1 gene cluster variation and BP-I. This polymorphism may contribute to genetic vulnerability through its possible role in neuron inflammation.
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Talaei
authors.affiliation: Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Jalil
authors.initials: J
authors.lastname: Tavakkol Afshari
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Fayyazi Bordbar
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Pouryousof
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Faridhosseini
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Saghebi
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Rezaei Ardani
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Andisheh
authors.initials: A
authors.lastname: Talaei
authors.affiliation: Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Tehrani
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D007492:Iran; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C508584:IL1A protein, human; C508585:IL1B protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta
keywords: Bipolar disorder; Interleukin 1 gene cluster; Iran; Polymorphism