Correlation of AQP4 gene polymorphism with NMO clinical phenotypes and its underlying mechanism

Objective To explore the correlation between aquaporin-4 (AQP4) gene single nucleotide polymorphism (SNP) and clinical phenotypes of neuromyelitis optica (NMO) and its underlying mechanism. Methods Eight SNPs in AQP4 gene regulatory region were selected and genotyped for 208 anti-AQP4 autoantibodies (NMO-IgG) seropositive cases during January 2010 to January 2014 and 204 healthy subjects. Then the correlation was further analysed between genotypes and NMO phenotypes. And the effect of microRNA (miRNA) on the expression of AQP4 gene was examined by dual-luciferase reporter technique. Results The A/T genotype of rs1058424 (50.61% vs 70.45%, OR=0.430, 95%CI 0.210–0.880) and C/T (50.00% vs 68.18%, OR=0.467, 95%CI 0.231–0.994) genotype of rs3763043 in 3′-UTR were correlated with longitudinal extensive transverse myelitis; the A/T genotype of rs1058424 (46.72% vs 66.28%, OR=0.525, 95%CI 0.276–0.999) and A/C genotype of rs335929 (45.08% vs 58.14%, OR=0.527, 95%CI 0.281–0.987) in 3′-UTR as well as C/T genotype of rs151244 (50.82% vs 69.77%, OR=0.450, 95%CI 0.230–0.881) in promoter 0 region were correlated with optic neuritis. The polymorphism of rs6508459 in 3′-UTR and rs3763040 in intron region were correlated with concurrent systemic autoimmune diseases (P=0.012 and 0.023 respectively). miRNA 323-3p could regulate AQP4 gene expression. However, variation in SNP rs1058424 failed to affect this regulation. Conclusion SNP in 3′-UTR of AQP4 gene may be associated with NMO phenotypes.miRNA 323-3p may participate in the pathogenesis of NMO by binding to certain SNP sites in 3′-UTR of AQP4 gene and regulating its expression. Key words: Neuromyelitis optica; Aquaporin-4 gene; 3′-untranslated region; MicroRNA