Associations of aquaporin-4 promoter polymorphism to multiple sclerosis and neuromyelitis optica in southern Chinese population

Abstract

Objective To investigate the associations of aquaporin-4 (AQP4) promoter polymorphisms with anti-AQP4 antibody and genetic susceptibility to multiple sclerosis (MS) and neuromyelitis optica (NMO) in Southern Chinese population. Methods The polymorphisms of AQP4 promoter 0 and 1 were analyzed by PCR and DNA sequencing in 18 NMO, 38 MS, 13 recurrent myelitis (RM), 6 recurrent optic neuritis (RON) patients and 39 healthy controls. Results Fourteen polymorphism loci were observed in AQP4-promoter 0, while 6 ones were observed in AQP4-promoter 1. Among them, the incidence rate of polymorphism at position -1003 bp (A-G) of AQP4-promoter 0 in anti-AQP4 antibody-positive patients was significantly higher than that in anti-AQP4 antibody-negative patients and controls (former: 13/18 vs 20/45, P=0.046; latter: 13/18 vs 10/39, P=0.001). The incidence rates of polymorphism at position between -401 bp and -400 bp (C inserted) of AQP4-promoter 1 in anti-AQP4 antibody-positive and -negative patients were significantly higher than that in controls(former: 5/16 vs 0/28, P=0.008；latter: 8/38 vs 0/28, P=0.027). The incidence rates of polymorphism at position -1003 bp (A-G) of AQP4-promoter 0 and position between -401 bp and -400 bp (C inserted) of AQP4-promoter 1 in patients with NMO and MS were significantly higher than that in controls( NMO：11/18 vs 10/39, P=0.010；4/15 vs 0/28, P=0.020；MS：19/38 vs 10/39, P=0.027；8/34 vs 0/28, P=0.018). Conclusions Polymorphisms loci were observed in AQP4-promoter 0 and AQP4-promoter 1, which may have an influence on the susceptibility to MS and NMO. Polymorphism at position -1003 bp (A-G) of AQP4-promoter 0 may be related to the emergence of anti-AQP4 antibody in patients with NMO and MS. Key words: Multiple sclerosis; Neuromyelitis optica; Aquaporin 4; Polymorphism; genetic