The single nucleotide polymorphism site of aquaporin-4 gene in patients with neuromyelitis optica

被引:10
|
作者
Wang, Qing-Song [1 ]
Xiao, Hong-Qiong [1 ]
Chen, Hua-Xian [1 ]
Liu, Yan-Ping [1 ]
Ding, Xu-Dong [1 ]
机构
[1] Hubei Univ Med, Xiangyang Peoples Hosp 1, Dept Rehabil Med, 15 Jiefang Rd, Xiangyang 441000, Hubei, Peoples R China
关键词
neuromyelitis optica; aquaporin-4; single nucleotide; polymorphism; BLOOD-BRAIN-BARRIER; MULTIPLE-SCLEROSIS; DIAGNOSTIC-CRITERIA; PATHOGENESIS; EXPRESSION; MARKER; EDEMA;
D O I
10.3892/etm.2017.5267
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The single nucleotide polymorphism (SNP) site within the aquaporin (AQP)-4 gene exons and its possible role in the pathogenesis of neuromyelitis optica (NMO) were studied. From March 2010 to June 2012, 72 patients with NMO from Xiangyang No. 1 People's Hospital, Hubei University of Medicine were enrolled in the NMO group. At the same time, 80 patients with multiple sclerosis (MS) were enrolled in our study as the MS group. Blood samples were collected and DNA was extracted for analysis of SNP sites of AQP4 gene. Specific site-directed mutagenesis method was used for site-directed mutagenesis on plasmid enhanced green fluorescence protein carrying AQP4 gene. Mutant plasmids were constructed and used for transfecting cell lines. The differences of anti-AQP4 antibody level in the cell line were analyzed. The possible correlation between AQP4 gene SNP sites and the pathogenesis of NMO were analyzed. In the NMO group, 6 SNP sites in AQP4 gene were located in exons 2 and 5. These included R108T, I110N, E280R, D281R, P295R and E317M. There was no SNP site in exons 1, 3 and 4. In the MS group, no SNP site was found in AQP4 gene. R108T, I110N, R108T/I110N, E280R/D281R, P295R and E317M cell lines were constructed in the NMO group, and anti-AQP4 antibody in the serum was compared between R108T/I110N, E280R/D281R and E317M cell lines and the original HEK293T cell line. The difference was statistically significant (P<0.05). The positive rate of anti-AQP4 antibody titer in serum was compared between R108T, I110N, R108T/I110N, E280R/D281R, P295R and E317M cell lines in the NMO group and the original cell line in the MS group. In conclusion, SNP sites in AQP4 gene in patients with NMO may lead to some conformational changes in AQP4 protein. This affects the antigenicity of AQP4 protein. The different intensity of antigen-antibody reaction may cause the differences of titer observed between the different mutant cell lines.
引用
收藏
页码:6017 / 6021
页数:5
相关论文
共 50 条
  • [11] Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica
    Jarius, Sven
    Paul, Friedemann
    Franciotta, Diego
    Waters, Patrick
    Zipp, Frauke
    Hohlfeld, Reinhard
    Vincent, Angela
    Wildemann, Brigitte
    NATURE CLINICAL PRACTICE NEUROLOGY, 2008, 4 (04): : 202 - 214
  • [12] Epidemiology of Aquaporin-4 Autoimmunity and Neuromyelitis Optica Spectrum
    Flanagan, Eoin P.
    Cabre, Philippe
    Weinshenker, Brian G.
    St Sauver, Jennifer
    Jacobson, Debra J.
    Majed, Masoud
    Lennon, Vanda A.
    Lucchinetti, Claudia F.
    McKeon, Andrew
    Matiello, Marcelo
    Kale, Nilifur
    Wingerchuk, Dean M.
    Mandrekar, Jay
    Sagen, Jessica A.
    Fryer, James P.
    Robinson, Angala Borders
    Pittock, Sean J.
    ANNALS OF NEUROLOGY, 2016, 79 (05) : 775 - 783
  • [13] Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients
    Gulsen Akman-Demir
    Erdem Tüzün
    Patrick Waters
    Sema İçöz
    Murat Kürtüncü
    Sven Jarius
    Zuhal Yapıcı
    Melike Mutlu
    Nilüfer Yeşilot
    Angela Vincent
    Mefkure Eraksoy
    Journal of Neurology, 2011, 258 : 464 - 470
  • [14] Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients
    Akman-Demir, Gulsen
    Tuzun, Erdem
    Waters, Patrick
    Icoz, Sema
    Kurtuncu, Murat
    Jarius, Sven
    Yapici, Zuhal
    Mutlu, Melike
    Yesilot, Nilufer
    Vincent, Angela
    Eraksoy, Mefkure
    JOURNAL OF NEUROLOGY, 2011, 258 (03) : 464 - 470
  • [15] Neuromyelitis optica in patients with gluten sensitivity associated with antibodies to aquaporin-4
    Jarius, S.
    Jacob, S.
    Waters, P.
    Jacob, A.
    Littleton, E.
    Vincent, A.
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2008, 79 (09): : 1084 - 1084
  • [16] Mechanisms of Disease: aquaporin-4 antibodies in neuromyelitis optica
    Sven Jarius
    Friedemann Paul
    Diego Franciotta
    Patrick Waters
    Frauke Zipp
    Reinhard Hohlfeld
    Angela Vincent
    Brigitte Wildemann
    Nature Clinical Practice Neurology, 2008, 4 : 202 - 214
  • [17] THE SPECTRUM OF NEUROMYELITIS OPTICA AND THE ROLE OF AQUAPORIN-4 ANTIBODIES
    O'Connor, Kevin D. J.
    Nolan, David
    Leong, W.
    John, Mina
    INTERNAL MEDICINE JOURNAL, 2014, 44 : 20 - 20
  • [18] Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders
    Kim, Sung-Min
    Waters, Patrick
    Woodhall, Mark
    Kim, Jee-Young
    Kim, Jee-Eun
    Yang, Ji Won
    Kim, Jun-Soon
    Sung, Jung-Joon
    Park, Kyung Seok
    Lee, Kwang-Woo
    MULTIPLE SCLEROSIS JOURNAL, 2013, 19 (08) : 1060 - 1067
  • [19] Endothelial damage in patients with neuromyelitis optica spectrum disorder with aquaporin-4 IgG
    Kuroda, Hiroshi
    Takai, Yoshiki
    Nishiyama, Shuhei
    Takahashi, Toshiyuki
    Misu, Tatsuro
    Nakashima, Ichiro
    Fujihara, Kazuo
    Aoki, Masashi
    MULTIPLE SCLEROSIS JOURNAL, 2020, 26 (09) : NP77 - NP78
  • [20] Autoantibodies to aquaporin-1 in Turkish neuromyelitis optica patients with and without aquaporin-4 antibodies
    Coban, A.
    Tzartos, J.
    Stergiou, C.
    Akman-Demir, G.
    Zisimopoulou, P.
    Shugaiv, E.
    Icoz, S.
    Tuzun, E.
    Kurtuncu, M.
    Eraksoy, M.
    Tzartos, S.
    MULTIPLE SCLEROSIS JOURNAL, 2013, 19 (11) : 85 - 86