A Study on the Association of Interleukin-1 Cluster with Genetic Risk in Bipolar I Disorder in Iranian Patients: A Case-control Study

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-1 alpha-889, IL-1 beta+3954, IL-1 beta-511, and IL-1RN (VNTR) were carried out using Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) and compared by SPSS using Fisher's exact and chi-square tests. The frequency of IL-1 beta-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.