Kaiyrzhanov Rauan, Aitkulova Akbota, Shashkin Chingiz, Zharkinbekova Nazira, Rizig Mie, Zholdybayeva Elena, Jarmukhanov Zharkyn, Akhmetzhanov Vadim, Kaishibayeva Gulnaz, Khaibullin Talgat, Karimova Altynay, Akshulakov Serik, Bralov Askhat, Kissamedenov Nurlan, Seidinova Zhanar, Taskinbayeva Anjela, Muratbaikyzy Aliya, Houlden Henry
University College London, Institute of Neurology, Department of Neuromuscular Disorders, Queen Square, WC1N 3BG, London, UK.
National Center for Biotechnology, Department of Molecular Genetics, 13/5 Korgalzhyn Avenue, 01000 Nur-Sultan, Kazakhstan.
Parkinsons Dis. 2020 Feb 19;2020:2763838. doi: 10.1155/2020/2763838. eCollection 2020.
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.
Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort.
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.
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, =0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, =0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5.
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.
亮氨酸重复激酶2（LRRK2）突变已成为帕金森病（PD）最常见且可能可治疗的决定因素。这些突变独特的地理分布引发了对不同种族背景的PD队列进行LRRK基因分型的兴趣。
在此，我们报告首个中亚PD队列中LRRK2筛查的结果。
来自哈萨克斯坦四个医疗中心的运动障碍专家连续招募了246例PD患者，并系统地获取了临床人口统计学数据和血液中的基因组DNA，与200名健康对照的DNA一起运往伦敦大学学院神经病学研究所。通过竞争性等位基因特异性聚合酶链反应分析，对该队列进行五个LRRK2突变（p.Gly2019Ser、p.Arg1441His、p.Tyr1699Cys、p.Ile2020Thr和p.Asn1437His）以及三个东亚疾病相关变异（p.Gly2385Arg、p.Ala419Val和p.Arg1628Pro）的基因分型。
研究对象均未携带LRRK2突变，而发现以下亚洲变异的优势比（OR）无统计学意义：p.Gly2385Arg（1.2%，次要等位基因频率（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）。
我们表明东亚LRRK变异可在中亚人群中发现，但其致病性仍有待在更大的PD队列中阐明。
