Case control study: G-allele of rs4244165 in JAK1 gene correlated with high-level brief psychiatric rating scale in bipolar patients

Bipolar disorder (BD) is a chronic and clinically complex disease, characterized by pathological disturbances in mood and energy. Cytokines can access the brain and their signaling pathways affect brain functions, such as neurotransmitter metabolism, neuroendocrine function, neural/synaptic plasticity, and mood neural circuitry. JAK 1 is the most common phosphorylation protein combined with the tyrosine kinase cytokine receptors; therefore, we investigated the association between the Janus family kinase 1 (JAK1) gene polymorphisms (rs2780895, rs4244165, and rs17127024) and susceptibility to BD. The case study population included 93 patients diagnosed with BD and 112 healthy controls, selected from the central coastal region of Tunisia. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate these 3 JAK1 polymorphisms. We compared the sociodemographic and clinical parameters of 3 genotypes of this single nucleotide polymorphisms rs2780895, rs4244165, and rs17127024 of the JAK1 gene. The frequencies of the 3 genotypes were similar in the patient and control groups. One-way analysis of variance revealed a significant variation in rs4244165. After hospitalization, the average of the brief psychiatric rating scale score was significantly higher for the wild-type GG genotype than that for the double-mutation TT genotype (31.23% vs 22.85%, P = .043). The least significant difference post hoc test also showed a significant difference between the GG and TT genotypes at both hospital admission (P = .001) and after hospitalization (P = .012), with the GG genotype being associated with a higher brief psychiatric rating scale score. Haplotypic analysis revealed that the wild-type haplotype with the highest frequency (46.62%) was CTG. Our results showed no association between the 3 studied positions and bipolar disorder. However, the G-allele of rs4244165 in JAK1 is associated with the highest level of the brief psychiatric rating scale in patients with bipolar disorder. The JAK/signal transducer and activator of transcription pathway is an interesting therapeutic route that requires further investigations. Studying their regulatory regions can provide a clearer picture of all the interactions involved in the regulation of genetic expression in response to treatment.