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Drug‐resistant epilepsy classified by a phenotyping algorithm associates with NTRK2.

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Title: Drug‐resistant epilepsy classified by a phenotyping algorithm associates with NTRK2.
Authors: Almoguera, Berta (AUTHOR), McGinnis, Emily (AUTHOR), Abrams, Debra (AUTHOR), Vazquez, Lyam (AUTHOR), Cederquist, Anna (AUTHOR), Sleiman, Patrick M. (AUTHOR), Dlugos, Dennis (AUTHOR), Hakonarson, Hakon (AUTHOR), Cagan, Andrew (AUTHOR), Connolly, John (AUTHOR), Gainer, Vivian S (AUTHOR), Garifallou, James (AUTHOR), Kaminski, Courtney (AUTHOR), Lee, Yvonne C. (AUTHOR), Mafra, Fernanda (AUTHOR), Mentch, Frank (AUTHOR), Pellegrino, Renata (AUTHOR), Qiu, Haijun (AUTHOR), Snyder, James (AUTHOR), Tian, Lifeng (AUTHOR)
Source: Acta Neurologica Scandinavica. Sep2019, Vol. 140 Issue 3, p169-176. 8p.
Subjects: Epilepsy, Ontogeny, Central nervous system, Drug resistance, Gene families, Pharmacogenomics
Abstract: Objective: Up to 40% of patients with epilepsy become drug resistant (DRE). Genetic factors are likely to play a role. While efforts have focused on the transporter and target hypotheses, neither of them fully explains the pan‐pharmacoresistance seen in DRE. Materials and methods: In this study, we developed and used a phenotyping algorithm for the identification of DRE, responders, and epilepsy‐free controls that were sequenced using a gene panel developed by the Pharmacogenomics Research Network (PGRN), which includes 82 genes involved in drug response. We tested the transporter hypothesis of DRE, the association between drug resistance and variants in the ATP‐binding cassette family of genes previously associated with DRE, and also investigated potential new genetic factors. Results: In the analysis of DRE vs controls, NTRK2 was significantly associated with DRE (rs76950094; P = 1.19 × 10−7 and gene‐based P‐value = 1.67 × 10−4). NTRK2 encodes TrkB, which is involved in the development and maturation of the central nervous system, and increased activation of TrkB signaling is suggested to promote epilepsy. Conclusion: Although the role of NTRK2 in DRE needs to be elucidated, these results support alternative mechanisms underlying DRE, complementary to the existing hypotheses, that should be evaluated. [ABSTRACT FROM AUTHOR]
Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Drug‐resistant epilepsy classified by a phenotyping algorithm associates with NTRK2.
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  Data: <searchLink fieldCode="AR" term="%22Almoguera%2C+Berta%22">Almoguera, Berta</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22McGinnis%2C+Emily%22">McGinnis, Emily</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Abrams%2C+Debra%22">Abrams, Debra</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vazquez%2C+Lyam%22">Vazquez, Lyam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cederquist%2C+Anna%22">Cederquist, Anna</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sleiman%2C+Patrick+M%2E%22">Sleiman, Patrick M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dlugos%2C+Dennis%22">Dlugos, Dennis</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hakonarson%2C+Hakon%22">Hakonarson, Hakon</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cagan%2C+Andrew%22">Cagan, Andrew</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Connolly%2C+John%22">Connolly, John</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gainer%2C+Vivian+S%22">Gainer, Vivian S</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Garifallou%2C+James%22">Garifallou, James</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kaminski%2C+Courtney%22">Kaminski, Courtney</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Yvonne+C%2E%22">Lee, Yvonne C.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mafra%2C+Fernanda%22">Mafra, Fernanda</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mentch%2C+Frank%22">Mentch, Frank</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pellegrino%2C+Renata%22">Pellegrino, Renata</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qiu%2C+Haijun%22">Qiu, Haijun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Snyder%2C+James%22">Snyder, James</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tian%2C+Lifeng%22">Tian, Lifeng</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Neurologica+Scandinavica%22">Acta Neurologica Scandinavica</searchLink>. Sep2019, Vol. 140 Issue 3, p169-176. 8p.
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  Data: <searchLink fieldCode="DE" term="%22Epilepsy%22">Epilepsy</searchLink><br /><searchLink fieldCode="DE" term="%22Ontogeny%22">Ontogeny</searchLink><br /><searchLink fieldCode="DE" term="%22Central+nervous+system%22">Central nervous system</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance%22">Drug resistance</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+families%22">Gene families</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacogenomics%22">Pharmacogenomics</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objective: Up to 40% of patients with epilepsy become drug resistant (DRE). Genetic factors are likely to play a role. While efforts have focused on the transporter and target hypotheses, neither of them fully explains the pan‐pharmacoresistance seen in DRE. Materials and methods: In this study, we developed and used a phenotyping algorithm for the identification of DRE, responders, and epilepsy‐free controls that were sequenced using a gene panel developed by the Pharmacogenomics Research Network (PGRN), which includes 82 genes involved in drug response. We tested the transporter hypothesis of DRE, the association between drug resistance and variants in the ATP‐binding cassette family of genes previously associated with DRE, and also investigated potential new genetic factors. Results: In the analysis of DRE vs controls, NTRK2 was significantly associated with DRE (rs76950094; P = 1.19 × 10−7 and gene‐based P‐value = 1.67 × 10−4). NTRK2 encodes TrkB, which is involved in the development and maturation of the central nervous system, and increased activation of TrkB signaling is suggested to promote epilepsy. Conclusion: Although the role of NTRK2 in DRE needs to be elucidated, these results support alternative mechanisms underlying DRE, complementary to the existing hypotheses, that should be evaluated. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ane.13115
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        Text: English
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        StartPage: 169
    Subjects:
      – SubjectFull: Epilepsy
        Type: general
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      – SubjectFull: Central nervous system
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      – SubjectFull: Pharmacogenomics
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