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 : 001C14 ( PubMed/Corpus ); précédent : 001C13; suivant : 001C15Association 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 ; Qingqing Dai ; Zhu Xu ; Dian He ; Hao Wang ; Qingsong Wang ; Yifan Zhang ; Yingwu Zhu ; Yuan Li ; Gang Cai ; Krantic Slavica ; Kermode AllanSource :
- 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
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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.</title><author><name sortKey="Chu, Lan" sort="Chu, Lan" uniqKey="Chu L" first="Lan" last="Chu">Lan Chu</name><affiliation><nlm: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.</nlm:affiliation></affiliation></author><author><name sortKey="Dai, Qingqing" sort="Dai, Qingqing" uniqKey="Dai Q" first="Qingqing" last="Dai">Qingqing Dai</name><affiliation><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></affiliation></author><author><name sortKey="Xu, Zhu" sort="Xu, Zhu" uniqKey="Xu Z" first="Zhu" last="Xu">Zhu Xu</name><affiliation><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></affiliation></author><author><name sortKey="He, Dian" sort="He, Dian" uniqKey="He D" first="Dian" last="He">Dian He</name><affiliation><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></affiliation></author><author><name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name><affiliation><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></affiliation></author><author><name sortKey="Wang, Qingsong" sort="Wang, Qingsong" uniqKey="Wang Q" first="Qingsong" last="Wang">Qingsong Wang</name><affiliation><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></affiliation></author><author><name sortKey="Zhang, Yifan" sort="Zhang, Yifan" uniqKey="Zhang Y" first="Yifan" last="Zhang">Yifan Zhang</name><affiliation><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></affiliation></author><author><name sortKey="Zhu, Yingwu" sort="Zhu, Yingwu" uniqKey="Zhu Y" first="Yingwu" last="Zhu">Yingwu Zhu</name><affiliation><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></affiliation></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><affiliation><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></affiliation></author><author><name sortKey="Cai, Gang" sort="Cai, Gang" uniqKey="Cai G" first="Gang" last="Cai">Gang Cai</name><affiliation><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></affiliation></author><author><name sortKey="Slavica, Krantic" sort="Slavica, Krantic" uniqKey="Slavica K" first="Krantic" last="Slavica">Krantic Slavica</name><affiliation><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></affiliation></author><author><name sortKey="Allan, Kermode" sort="Allan, Kermode" uniqKey="Allan K" first="Kermode" last="Allan">Kermode Allan</name><affiliation><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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:25895050</idno><idno type="pmid">25895050</idno><idno type="doi">10.1007/s12035-015-9171-9</idno><idno type="wicri:Area/PubMed/Corpus">001C14</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001C14</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">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.</title><author><name sortKey="Chu, Lan" sort="Chu, Lan" uniqKey="Chu L" first="Lan" last="Chu">Lan Chu</name><affiliation><nlm: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.</nlm:affiliation></affiliation></author><author><name sortKey="Dai, Qingqing" sort="Dai, Qingqing" uniqKey="Dai Q" first="Qingqing" last="Dai">Qingqing Dai</name><affiliation><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></affiliation></author><author><name sortKey="Xu, Zhu" sort="Xu, Zhu" uniqKey="Xu Z" first="Zhu" last="Xu">Zhu Xu</name><affiliation><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></affiliation></author><author><name sortKey="He, Dian" sort="He, Dian" uniqKey="He D" first="Dian" last="He">Dian He</name><affiliation><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></affiliation></author><author><name sortKey="Wang, Hao" sort="Wang, Hao" uniqKey="Wang H" first="Hao" last="Wang">Hao Wang</name><affiliation><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></affiliation></author><author><name sortKey="Wang, Qingsong" sort="Wang, Qingsong" uniqKey="Wang Q" first="Qingsong" last="Wang">Qingsong Wang</name><affiliation><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></affiliation></author><author><name sortKey="Zhang, Yifan" sort="Zhang, Yifan" uniqKey="Zhang Y" first="Yifan" last="Zhang">Yifan Zhang</name><affiliation><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></affiliation></author><author><name sortKey="Zhu, Yingwu" sort="Zhu, Yingwu" uniqKey="Zhu Y" first="Yingwu" last="Zhu">Yingwu Zhu</name><affiliation><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></affiliation></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><affiliation><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></affiliation></author><author><name sortKey="Cai, Gang" sort="Cai, Gang" uniqKey="Cai G" first="Gang" last="Cai">Gang Cai</name><affiliation><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></affiliation></author><author><name sortKey="Slavica, Krantic" sort="Slavica, Krantic" uniqKey="Slavica K" first="Krantic" last="Slavica">Krantic Slavica</name><affiliation><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></affiliation></author><author><name sortKey="Allan, Kermode" sort="Allan, Kermode" uniqKey="Allan K" first="Kermode" last="Allan">Kermode Allan</name><affiliation><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></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><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">25895050</PMID><DateCreated><Year>2016</Year><Month>06</Month><Day>11</Day></DateCreated><DateRevised><Year>2017</Year><Month>11</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1559-1182</ISSN><JournalIssue CitedMedium="Internet"><Volume>53</Volume><Issue>5</Issue><PubDate><Year>2016</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Molecular neurobiology</Title><ISOAbbreviation>Mol. Neurobiol.</ISOAbbreviation></Journal><ArticleTitle>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.</ArticleTitle><Pagination><MedlinePgn>2878-2885</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s12035-015-9171-9</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chu</LastName><ForeName>Lan</ForeName><Initials>L</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dai</LastName><ForeName>Qingqing</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Zhu</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Dian</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Hao</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Qingsong</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yifan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Yingwu</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Gang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Neurology, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Slavica</LastName><ForeName>Krantic</ForeName><Initials>K</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allan</LastName><ForeName>Kermode</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Australian Neuromuscular Research Institute, Centre for Neuromuscular and Neurological Disorders, SJOG Clinic, Suite 314, 25 McCourt St Subiaco, Perth, WA, 6008, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>04</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Neurobiol</MedlineTA><NlmUniqueID>8900963</NlmUniqueID><ISSNLinking>0893-7648</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>Mol Neurobiol. 2016 Jul;53(5):2886</RefSource><PMID Version="1">26553348</PMID></CommentsCorrections><CommentsCorrections 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