Preliminary study on the association of AQP4 promoter polymorphism with anti-aquaporin-4 antibody positivity in southern Han Chinese patients with idiopathic demyelinating disorders of central nervous system

J Neuroimmunol. 2013 Feb 15;255(1-2):75-80. doi: 10.1016/j.jneuroim.2012.10.004. Epub 2012 Oct 29.

Abstract

Objectives: To identify the association of aquaporin-4 (AQP4) promoter polymorphism with the presence of anti-aquaporin-4 antibody (AQP4-Ab) in Southern Han Chinese patients with idiopathic demyelinating disorders of central nervous system.

Methods: Eighteen neuromyelitis optica (NMO), thirty-eight conventional MS (CMS), thirteen recurrent myelitis (RM), six recurrent optic neuritis (RON) patients and thirty-nine matched controls were enrolled. Polymorphisms of AQP4 promoters 0 and 1 were determined by sequencing-based typing.

Results: Fourteen polymorphism loci were observed in AQP4-promoter 0, while the six ones were observed in AQP4-promoter 1. Among them, the frequency of polymorphism at position -1003bp (A-G) of AQP4-promoter 0 in AQP4-Ab-positive patients was significantly higher than that in AQP4-Ab-negative patients and controls (former: 13/18 vs 20/45, P=0.046; latter: 13/18 vs 10/39, P=.001). The frequency of polymorphism at position between -401bp and -400bp (C inserted) of AQP4-promoter 1 in AQP4-Ab-positive and -negative patients was significantly higher than that in controls (former: 5/16 vs 0/28, P=0.008; latter: 8/38 vs 0/28, P=0.027).

Conclusions: Polymorphism at position -1003bp (A-G) of AQP4-promoter 0 is associated with the presence of anti-AQP4 antibody. Genetic variation in AQP4 may account for the susceptibility to AQP4-Ab-positive NMO and NMO spectrum disorders in Southern Han Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aquaporin 4 / genetics*
  • Aquaporin 4 / immunology*
  • Asian People / genetics
  • Autoantibodies / biosynthesis*
  • Female
  • Hereditary Central Nervous System Demyelinating Diseases / epidemiology
  • Hereditary Central Nervous System Demyelinating Diseases / genetics*
  • Hereditary Central Nervous System Demyelinating Diseases / immunology
  • Humans
  • Male
  • Middle Aged
  • Neuromyelitis Optica / ethnology
  • Neuromyelitis Optica / genetics*
  • Neuromyelitis Optica / immunology*
  • Pilot Projects
  • Polymorphism, Genetic / genetics
  • Polymorphism, Genetic / immunology
  • Promoter Regions, Genetic / immunology*
  • Young Adult

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies