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.
Identifieur interne : 002335 ( Main/Exploration ); précédent : 002334; suivant : 002336Association 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.
Auteurs : Lan Chu [République populaire de Chine] ; Qingqing Dai [République populaire de Chine] ; Zhu Xu [République populaire de Chine] ; Dian He [République populaire de Chine] ; Hao Wang [République populaire de Chine] ; Qingsong Wang [République populaire de Chine] ; Yifan Zhang [République populaire de Chine] ; Yingwu Zhu [République populaire de Chine] ; Yuan Li [République populaire de Chine] ; Gang Cai [République populaire de Chine] ; Krantic Slavica [France] ; Kermode Allan [Australie]Source :
- Molecular neurobiology [ 1559-1182 ] ; 2016.
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.
DOI: 10.1007/s12035-015-9171-9
PubMed: 25895050
Affiliations:
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Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yifan" sort="Zhang, Yifan" uniqKey="Zhang Y" first="Yifan" last="Zhang">Yifan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Yingwu" sort="Zhu, Yingwu" uniqKey="Zhu Y" first="Yingwu" last="Zhu">Yingwu Zhu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de 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Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Dai, Qingqing" sort="Dai, Qingqing" uniqKey="Dai Q" first="Qingqing" last="Dai">Qingqing Dai</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Zhu" sort="Xu, Zhu" uniqKey="Xu Z" first="Zhu" last="Xu">Zhu Xu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="He, Dian" sort="He, Dian" uniqKey="He D" first="Dian" last="He">Dian He</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Qingsong" sort="Wang, Qingsong" uniqKey="Wang Q" first="Qingsong" last="Wang">Qingsong Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yifan" sort="Zhang, Yifan" uniqKey="Zhang Y" first="Yifan" last="Zhang">Yifan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Yingwu" sort="Zhu, Yingwu" uniqKey="Zhu Y" first="Yingwu" last="Zhu">Yingwu Zhu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Gang" sort="Cai, Gang" uniqKey="Cai G" first="Gang" last="Cai">Gang Cai</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province</wicri:regionArea><wicri:noRegion>Guizhou Province</wicri:noRegion></affiliation></author><author><name sortKey="Slavica, Krantic" sort="Slavica, Krantic" uniqKey="Slavica K" first="Krantic" last="Slavica">Krantic Slavica</name><affiliation wicri:level="3"><nlm: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.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Pierre et Marie Currie (Paris V), Centre de, Recherche des Cordeliers (CRC), 15, Rue de l'Ecole de Médecine, 75 006, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Allan, Kermode" sort="Allan, Kermode" uniqKey="Allan K" first="Kermode" last="Allan">Kermode Allan</name><affiliation wicri:level="1"><nlm:affiliation>Australian Neuromuscular Research Institute, Centre for Neuromuscular and Neurological Disorders, SJOG Clinic, Suite 314, 25 McCourt St Subiaco, Perth, WA, 6008, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Neuromuscular Research Institute, Centre for Neuromuscular and Neurological Disorders, SJOG Clinic, Suite 314, 25 McCourt St Subiaco, Perth, WA, 6008</wicri:regionArea><wicri:noRegion>6008</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular neurobiology</title><idno type="eISSN">1559-1182</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>République populaire de Chine</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chu, Lan" sort="Chu, Lan" uniqKey="Chu L" first="Lan" last="Chu">Lan Chu</name></noRegion><name sortKey="Cai, Gang" sort="Cai, Gang" uniqKey="Cai G" first="Gang" last="Cai">Gang Cai</name><name sortKey="Dai, Qingqing" sort="Dai, Qingqing" uniqKey="Dai Q" first="Qingqing" last="Dai">Qingqing Dai</name><name sortKey="He, Dian" sort="He, Dian" uniqKey="He D" first="Dian" last="He">Dian He</name><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name><name sortKey="Wang, Qingsong" sort="Wang, Qingsong" uniqKey="Wang Q" first="Qingsong" last="Wang">Qingsong Wang</name><name sortKey="Xu, Zhu" sort="Xu, Zhu" uniqKey="Xu Z" first="Zhu" last="Xu">Zhu Xu</name><name sortKey="Zhang, Yifan" sort="Zhang, Yifan" uniqKey="Zhang Y" first="Yifan" last="Zhang">Yifan Zhang</name><name sortKey="Zhu, Yingwu" sort="Zhu, Yingwu" uniqKey="Zhu Y" first="Yingwu" last="Zhu">Yingwu Zhu</name></country><country name="France"><region name="Île-de-France"><name sortKey="Slavica, Krantic" sort="Slavica, Krantic" uniqKey="Slavica K" first="Krantic" last="Slavica">Krantic Slavica</name></region></country><country name="Australie"><noRegion><name sortKey="Allan, Kermode" sort="Allan, Kermode" uniqKey="Allan K" first="Kermode" last="Allan">Kermode Allan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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