IL-1α, IL-1β and IL-1RN haplotypes are associated with bipolar I disorder and its characteristics: A pilot case-control study

Background

Bipolar I disorder (BID) is a severe psychiatric disease with a confirmed strong hereditary pattern. However, the genetic component is not completely clear to design the diagnostic tests. In this pilot study, we aimed to evaluate the association of haplotypes, including four polymorphisms in the IL-1 region, with BID in a sample of the Iranian population.

Methods

In a case-control study, genotyping of 95 subjects (48 BID and 47 healthy samples) were performed using PCR-based methods for IL-1α (rs1800587), IL-1b +3954 (rs1143634), IL-1b −511 (rs16944) and IL-1RN (VNTR; rs2234663) loci. PHASE was used for haplotyping, and data were analyzed using SPSS 16.

Results

Out of 55 haplotypes and 121 diplotypes, three haplotypes including two SNPs (C-T of rs1800587-rs16944, p = 0.007, T-C of rs1143634-rs16944, p = 0.044 and T-A1 of rs16944-rs2234663, p = 0.030) and one haplotype including three SNPs (C-C-T of rs1800587-rs1143634-rs16944, p = 0.012) and one diplotype including two SNPs (C-T/C-T of rs1800587-rs16944, p = 0.032) were identified to be associated with the risk of the disease. In addition, several haplotypes and diplotypes were associated with the disease's features, including the age of onset, the type of first episode and the history of depressive episodes.

Conclusion

Our findings suggest a diagnostic role of the interleukin-1 region in the BID. The risky haplotypes may carry one or more susceptibility alleles, and the evaluation of their action will aid individual-level risk prediction.