title: Association Between the Single Nucleotide Polymorphism and the Level of Aquaporin-4 Protein Expression in Han and Minority Chinese with Inflammatory Demyelinating Diseases of the Central Nervous System.
abstract: The purpose of this study was to determine whether or not aquaporin-4 (AQP4) gene mutations are related to the pathogenesis of inflammatory demyelinating diseases in the central nervous system. Polymorphisms of AQP4 exons 1-5 were determined by sequencing DNA from 67 patients with central nervous system inflammatory demyelinating diseases, including neuromyelitis optica (NMO), multiple sclerosis, recurrent or simultaneous bilateral optic neuritis, and longitudinally extensive transverse myelitis. A plasmid with the identified new missense mutation was constructed, and human embryonic kidney cells (HEK293A) were transfected with either the pEGFP-N1-AQP4-M23 vector (bearing the identified mutated cDNA sequence) or with the plasmid bearing the wild-type AQP4 gene sequence. AQP4 protein expression was analyzed in both experimental groups using Western Blot analysis following protein extraction from transfected cells. A synonymous mutation (rs1839318) was detected on exon 3, and an additional synonymous mutation was detected on the exon 2-2 (rs72557968). Most importantly, a new missense mutation was detected on exon 2-1. According to Western blot analysis, the mutated cDNA sequence yielded increased AQP4 protein expression in comparison with the wild-type cDNA sequence (P < 0.05). AQP4 gene mutations are uncommon, occurring in only 3 out of 67 patients. Although it is possible that the mutations contributed to an increased risk of inflammatory central nervous system disease in these individuals, it is unlikely that mutations are a significant contributor to most patients with NMO spectrum disorders in China.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China. daisyqq929@yeah.net.
authors.forename: Lan
authors.initials: L
authors.lastname: Chu
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Dian
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Yingwu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cai
authors.affiliation: Université Pierre et Marie Currie (Paris V), Centre de, Recherche des Cordeliers (CRC), 15, Rue de l'Ecole de Médecine, 75 006, Paris, France.
authors.forename: Krantic
authors.initials: K
authors.lastname: Slavica
authors.affiliation: Australian Neuromuscular Research Institute, Centre for Neuromuscular and Neurological Disorders, SJOG Clinic, Suite 314, 25 McCourt St Subiaco, Perth, WA, 6008, Australia.
authors.forename: Kermode
authors.initials: K
authors.lastname: Allan
mesh_terms: D000328:Adult; D000906:Antibodies / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D020278:Demyelinating Autoimmune Diseases, CNS / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D008913:Minority Groups; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000906:Antibodies; D051401:Aquaporin 4
keywords: Aquaporin-4; Inflammatory demyelinating diseases; Neuromyelitis optica; Orthogonal arrays of particles; Single nucleotide polymorphisms