Bipolar disorder (BD) is a cyclical and chronic affective disorder, globally recognized as an important public health problem and characterized by mood changes with recurring phases such as mania and depression. It is considered a complex disease, depending on the interaction of genetic and environmental triggers (stressors factors), but with a poorly known pathogenesis. Recent studies have implicated immune factors in the pathogenesis of BD and more particularly associated with different human major histocompatibility complex (MHC) regions. A major consortium study have recently linked BD to hundreds of variations with stronger associations in the MHC region, such as the rs3130297 SNP, located in the NOTCH4 gene, with an additional overlapping association with schizophrenia. This short review focuses on studies that investigated the association between bipolar disorder and the MHC, and the involvement of the immune system in the pathogenesis of the disease, in order to provide further information for additional diagnostic and therapeutic strategies. Fully understanding the etiology and pathophysiology of BD is extremely important to define new approaches for intervention and prevention, maybe through the modulation of the immune system.

We propose a bioinformatics pipeline in which we use an ESTs database to predict and validate single-nucleotide polymorphisms (SNPs) directly linked to gene-coding regions at the HLA class I genes (HLA-A, HLA-B and HLA-C). Annotation originated from our analysis revealed various classes of possible new variations that may indicate possible new alleles. Thus, bioinformatics pipelines seem to be useful approaches to help screening for novel genetic variations at the HLA panel, and further analysis will foster this aim to provide celerity at the massive analysis of data currently generated in large-scale high-throughput experiments.