LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan
Background. LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson’s disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK. Objective. Here, we repo...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2020/2763838 |
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| author | Rauan Kaiyrzhanov Akbota Aitkulova Chingiz Shashkin Nazira Zharkinbekova Mie Rizig Elena Zholdybayeva Zharkyn Jarmukhanov Vadim Akhmetzhanov Gulnaz Kaishibayeva Talgat Khaibullin Altynay Karimova Serik Akshulakov Askhat Bralov Nurlan Kissamedenov Zhanar Seidinova Anjela Taskinbayeva Aliya Muratbaikyzy Henry Houlden |
| author_facet | Rauan Kaiyrzhanov Akbota Aitkulova Chingiz Shashkin Nazira Zharkinbekova Mie Rizig Elena Zholdybayeva Zharkyn Jarmukhanov Vadim Akhmetzhanov Gulnaz Kaishibayeva Talgat Khaibullin Altynay Karimova Serik Akshulakov Askhat Bralov Nurlan Kissamedenov Zhanar Seidinova Anjela Taskinbayeva Aliya Muratbaikyzy Henry Houlden |
| author_sort | Rauan Kaiyrzhanov |
| collection | DOAJ |
| description | Background. LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson’s disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK. Objective. Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort. Methods. 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis. Results. None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, p=0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, p=0.4), and p.Arg1628Pro was found only in 1% of controls. p.Gly2385Arg was positive in a big family with PD and tremor, although with incomplete segregation. One early-onset PD subject was homozygous for p.Ala419Val who developed fast progression and severe dyskinesias. p.Ala419Val was associated with early-onset PD. Conclusions. We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts. |
| format | Article |
| id | doaj-art-e1290314fb6d4c18a782d814d7b74bc4 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-e1290314fb6d4c18a782d814d7b74bc42025-02-03T05:54:26ZengWileyParkinson's Disease2090-80832042-00802020-01-01202010.1155/2020/27638382763838LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from KazakhstanRauan Kaiyrzhanov0Akbota Aitkulova1Chingiz Shashkin2Nazira Zharkinbekova3Mie Rizig4Elena Zholdybayeva5Zharkyn Jarmukhanov6Vadim Akhmetzhanov7Gulnaz Kaishibayeva8Talgat Khaibullin9Altynay Karimova10Serik Akshulakov11Askhat Bralov12Nurlan Kissamedenov13Zhanar Seidinova14Anjela Taskinbayeva15Aliya Muratbaikyzy16Henry Houlden17University College London, Institute of Neurology, Department of Neuromuscular Disorders, Queen Square, WC1N 3BG, London, UKNational Center for Biotechnology, Department of Molecular Genetics, 13/5 Korgalzhyn Avenue, 01000 Nur-Sultan, KazakhstanSouth Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, KazakhstanSouth Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, KazakhstanUniversity College London, Institute of Neurology, Department of Neuromuscular Disorders, Queen Square, WC1N 3BG, London, UKNational Center for Biotechnology, Department of Molecular Genetics, 13/5 Korgalzhyn Avenue, 01000 Nur-Sultan, KazakhstanNational Center for Biotechnology, Department of Molecular Genetics, 13/5 Korgalzhyn Avenue, 01000 Nur-Sultan, KazakhstanSouth Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, KazakhstanInstitute of Neurology Named After S. K. Kaishibayev, 9a Mamur 4 Micro-district, 050000 Almaty, KazakhstanSemey Medical University, Department of Neurology, 103 Abai Street, 071400 Semey, KazakhstanInstitute of Neurology Named After S. K. Kaishibayev, 9a Mamur 4 Micro-district, 050000 Almaty, KazakhstanNational Center for Neurosurgery, 34/1 Turan Avenue, 01000 Nur-Sultan, KazakhstanNational Center for Neurosurgery, 34/1 Turan Avenue, 01000 Nur-Sultan, KazakhstanNational Center for Neurosurgery, 34/1 Turan Avenue, 01000 Nur-Sultan, KazakhstanSouth Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, KazakhstanSouth Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, KazakhstanSouth Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, KazakhstanUniversity College London, Institute of Neurology, Department of Neuromuscular Disorders, Queen Square, WC1N 3BG, London, UKBackground. LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson’s disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK. Objective. Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort. Methods. 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis. Results. None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, p=0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, p=0.4), and p.Arg1628Pro was found only in 1% of controls. p.Gly2385Arg was positive in a big family with PD and tremor, although with incomplete segregation. One early-onset PD subject was homozygous for p.Ala419Val who developed fast progression and severe dyskinesias. p.Ala419Val was associated with early-onset PD. Conclusions. We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts.http://dx.doi.org/10.1155/2020/2763838 |
| spellingShingle | Rauan Kaiyrzhanov Akbota Aitkulova Chingiz Shashkin Nazira Zharkinbekova Mie Rizig Elena Zholdybayeva Zharkyn Jarmukhanov Vadim Akhmetzhanov Gulnaz Kaishibayeva Talgat Khaibullin Altynay Karimova Serik Akshulakov Askhat Bralov Nurlan Kissamedenov Zhanar Seidinova Anjela Taskinbayeva Aliya Muratbaikyzy Henry Houlden LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan Parkinson's Disease |
| title | LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan |
| title_full | LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan |
| title_fullStr | LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan |
| title_full_unstemmed | LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan |
| title_short | LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan |
| title_sort | lrrk2 mutations and asian disease associated variants in the first parkinson s disease cohort from kazakhstan |
| url | http://dx.doi.org/10.1155/2020/2763838 |
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