Analysis of Association between MAP2K4 Gene Polymorphism rs3826392 and IL-1b Serum Level in Southern Chinese Han Ischemic Stroke Patients.

BACKGROUND

Mitogen-activated protein kinase kinase 4 (MAP2K4) gene acts as the direct upstream activator of c-Jun NH2-terminal kinase pathway, which plays an important role in regulating neuron survival and apoptosis in response to cerebral ischemia. However, the association between MAP2K4 gene polymorphisms and ischemic stroke (IS) has not yet been published. Therefore, this study investigates the association between MAP2K4 gene polymorphism rs3826392 and IS susceptibility, as well as its quantitative traits in Southern Chinese Han population.

METHODS

A total of 816 Chinese patients with IS and 816 age- and sex-matched controls were recruited. Rs3826392 was genotyped using Sequenom MassARRAY iPLEX platform (Sequenom, San Diego, CA, USA). The mRNA expression of MAP2K4 gene in peripheral blood mononuclear cells was detected using reverse transcription-polymerase chain reaction. The levels of serum cytokines, including IL-1b, IL-6, IL-8, IL-12, and tumor necrosis factor-α (TNF-α), were measured by enzyme-linked immunosorbent assay.

RESULTS

Significant association was not observed between MAP2K4 gene polymorphism rs3826392 and IS susceptibility in all genetic models (P > .05). A significant difference was found in IL-1b, IL-6, IL-8, and TNF-α serum levels between patients with IS and control groups. MAP2K4 gene polymorphism rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels compared with AA genotype carriers (P = .029) in patients with IS.

CONCLUSION

MAP2K4 gene polymorphism rs3826392 did not contribute to IS susceptibility, but rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels. This result suggests that rs3826392 may play a potential role in the IS inflammatory process.