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Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity
Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are invo...
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| Published in: | Neuromolecular medicine 2010-09, Vol.12 (3), p.292-299 |
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| creator | von Spiczak, Sarah Muhle, Hiltrud Helbig, Ingo de Kovel, Carolien G. F. Hampe, Jochen Gaus, Verena Koeleman, Bobby P. C. Lindhout, Dick Schreiber, Stefan Sander, Thomas Stephani, Ulrich |
| description | Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the
TRPC4
gene. Thirty-five single nucleotide polymorphisms (SNP) within
TRPC4
were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV;
n
= 273), a narrow model of affectedness (PPR types III and IV;
n
= 214) and PPR associated with IGE (PPR/IGE;
n
= 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (
P
= 0.005) and haplotype level (
P
= 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at
P
|
| doi_str_mv | 10.1007/s12017-010-8122-x |
| format | article |
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TRPC4
gene. Thirty-five single nucleotide polymorphisms (SNP) within
TRPC4
were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV;
n
= 273), a narrow model of affectedness (PPR types III and IV;
n
= 214) and PPR associated with IGE (PPR/IGE;
n
= 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (
P
= 0.005) and haplotype level (
P
= 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at
P
< 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni–Holm for haplotypes. No association was found between variants in
TRPC4
and other phenotypes. Our results showed a trend toward association of
TRPC4
variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance of
TRPC4
for PPR and IGE.</description><identifier>ISSN: 1535-1084</identifier><identifier>EISSN: 1559-1174</identifier><identifier>DOI: 10.1007/s12017-010-8122-x</identifier><identifier>PMID: 20574736</identifier><language>eng</language><publisher>New York: Humana Press Inc</publisher><subject>Base Sequence ; Biomedical and Life Sciences ; Biomedicine ; Epilepsy, Generalized - genetics ; Epilepsy, Reflex - genetics ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Internal Medicine ; Neurology ; Neurosciences ; Original Paper ; Photic Stimulation ; Polymorphism, Single Nucleotide ; TRPC Cation Channels - genetics</subject><ispartof>Neuromolecular medicine, 2010-09, Vol.12 (3), p.292-299</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-52bf49c456bb629c84edeea5bb4f3b1b28f7fc9bd3157d77b219aebe93ce744f3</citedby><cites>FETCH-LOGICAL-c445t-52bf49c456bb629c84edeea5bb4f3b1b28f7fc9bd3157d77b219aebe93ce744f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20574736$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>von Spiczak, Sarah</creatorcontrib><creatorcontrib>Muhle, Hiltrud</creatorcontrib><creatorcontrib>Helbig, Ingo</creatorcontrib><creatorcontrib>de Kovel, Carolien G. F.</creatorcontrib><creatorcontrib>Hampe, Jochen</creatorcontrib><creatorcontrib>Gaus, Verena</creatorcontrib><creatorcontrib>Koeleman, Bobby P. C.</creatorcontrib><creatorcontrib>Lindhout, Dick</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Sander, Thomas</creatorcontrib><creatorcontrib>Stephani, Ulrich</creatorcontrib><title>Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity</title><title>Neuromolecular medicine</title><addtitle>Neuromol Med</addtitle><addtitle>Neuromolecular Med</addtitle><description>Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the
TRPC4
gene. Thirty-five single nucleotide polymorphisms (SNP) within
TRPC4
were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV;
n
= 273), a narrow model of affectedness (PPR types III and IV;
n
= 214) and PPR associated with IGE (PPR/IGE;
n
= 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (
P
= 0.005) and haplotype level (
P
= 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at
P
< 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni–Holm for haplotypes. No association was found between variants in
TRPC4
and other phenotypes. Our results showed a trend toward association of
TRPC4
variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance of
TRPC4
for PPR and IGE.</description><subject>Base Sequence</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Epilepsy, Generalized - genetics</subject><subject>Epilepsy, Reflex - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Internal Medicine</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Original Paper</subject><subject>Photic Stimulation</subject><subject>Polymorphism, Single Nucleotide</subject><subject>TRPC Cation Channels - genetics</subject><issn>1535-1084</issn><issn>1559-1174</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkVFLHDEQx4NU1Go_gC8l9MWn1Uw2uWwe5VBbEJSqjxKS3VmN7G3OJNt6_fTN9WwLBelTBvKb_8zwI-QQ2DEwpk4ScAaqYsCqBjivXrbIHkipKwAl3q3rWlbAGrFL3qf0xBjnALBDdjmTSqh6tkfuT1MKrbfZh5He5Klb0dDT26_Xc0FtopbO7dj5zmakFzgi7UP8VUQ7-B_Y0bOlH3CZVvS7z4_0-jHkkHBMPvtvPq8OyHZvh4QfXt99cnd-djv_XF1eXXyZn15WrRAyV5K7XuhWyJlzM67bRmCHaKVzoq8dON70qm-162qQqlPKcdAWHeq6RSUKs0-ONrnLGJ4nTNksfGpxGOyIYUpGM16Lhiv5X1KJRiuppCjkp3_IpzDFsZxhGlX2mGloCgQbqI0hpYi9WUa_sHFlgJm1I7NxZIojs3ZkXkrPx9fgyS2w-9PxW0oB-AZI5Wt8wPh38tupPwGvrJy9</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>von Spiczak, Sarah</creator><creator>Muhle, Hiltrud</creator><creator>Helbig, Ingo</creator><creator>de Kovel, Carolien G. 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C.</creator><creator>Lindhout, Dick</creator><creator>Schreiber, Stefan</creator><creator>Sander, Thomas</creator><creator>Stephani, Ulrich</creator><general>Humana Press Inc</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>7T7</scope><scope>C1K</scope><scope>RC3</scope></search><sort><creationdate>20100901</creationdate><title>Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity</title><author>von Spiczak, Sarah ; Muhle, Hiltrud ; Helbig, Ingo ; de Kovel, Carolien G. 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F.</au><au>Hampe, Jochen</au><au>Gaus, Verena</au><au>Koeleman, Bobby P. C.</au><au>Lindhout, Dick</au><au>Schreiber, Stefan</au><au>Sander, Thomas</au><au>Stephani, Ulrich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity</atitle><jtitle>Neuromolecular medicine</jtitle><stitle>Neuromol Med</stitle><addtitle>Neuromolecular Med</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>12</volume><issue>3</issue><spage>292</spage><epage>299</epage><pages>292-299</pages><issn>1535-1084</issn><eissn>1559-1174</eissn><abstract>Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the
TRPC4
gene. Thirty-five single nucleotide polymorphisms (SNP) within
TRPC4
were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV;
n
= 273), a narrow model of affectedness (PPR types III and IV;
n
= 214) and PPR associated with IGE (PPR/IGE;
n
= 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (
P
= 0.005) and haplotype level (
P
= 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at
P
< 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni–Holm for haplotypes. No association was found between variants in
TRPC4
and other phenotypes. Our results showed a trend toward association of
TRPC4
variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance of
TRPC4
for PPR and IGE.</abstract><cop>New York</cop><pub>Humana Press Inc</pub><pmid>20574736</pmid><doi>10.1007/s12017-010-8122-x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| subjects | Base Sequence Biomedical and Life Sciences Biomedicine Epilepsy, Generalized - genetics Epilepsy, Reflex - genetics Genetic Predisposition to Disease Genotype Haplotypes Internal Medicine Neurology Neurosciences Original Paper Photic Stimulation Polymorphism, Single Nucleotide TRPC Cation Channels - genetics |
| title | Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity |
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