LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson's Disease Cohort from Kazakhstan

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

doi:10.1155/2020/2763838

LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson's Disease Cohort from Kazakhstan

Parkinsons Dis. 2020 Feb 19:2020:2763838. doi: 10.1155/2020/2763838. eCollection 2020.

Authors

Rauan Kaiyrzhanov¹, Akbota Aitkulova², Chingiz Shashkin³, Nazira Zharkinbekova³, Mie Rizig¹, Elena Zholdybayeva², Zharkyn Jarmukhanov², Vadim Akhmetzhanov³, Gulnaz Kaishibayeva⁴, Talgat Khaibullin⁵, Altynay Karimova⁴, Serik Akshulakov⁶, Askhat Bralov⁶, Nurlan Kissamedenov⁶, Zhanar Seidinova³, Anjela Taskinbayeva³, Aliya Muratbaikyzy³, Henry Houlden¹

Affiliations

¹ University College London, Institute of Neurology, Department of Neuromuscular Disorders, Queen Square, WC1N 3BG, London, UK.
² National Center for Biotechnology, Department of Molecular Genetics, 13/5 Korgalzhyn Avenue, 01000 Nur-Sultan, Kazakhstan.
³ South Kazakhstan Medical Academy, Department of Neurology, 1/1Al-Farabi Avenue, 160019 Shymkent, Kazakhstan.
⁴ Institute of Neurology Named After S. K. Kaishibayev, 9a Mamur 4 Micro-district, 050000 Almaty, Kazakhstan.
⁵ Semey Medical University, Department of Neurology, 103 Abai Street, 071400 Semey, Kazakhstan.
⁶ National Center for Neurosurgery, 34/1 Turan Avenue, 01000 Nur-Sultan, Kazakhstan.

Abstract

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=0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5.

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.

Abstract

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