Neurology Unit, Department of Medicine, Faculty of Clinical Sciences, College of Medicine, University of Lagos & Lagos University Teaching Hospital, Idi Araba, Lagos State, Nigeria.
Department of Molecular Neuroscience, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
PLoS One. 2018 Dec 3;13(12):e0207984. doi: 10.1371/journal.pone.0207984. eCollection 2018.
To date the LRRK2 p.G2019S mutation remains the most common genetic cause of Parkinson disease (PD) worldwide. It accounts for up to 6% of familial and approximately 1.5% of sporadic cases. LRRK2 has a kinase enzymatic domain which provides an attractive potential target for drug therapies and LRRK2 kinase inhibitors are in development. Prevalence of the p.G2019S has a variable ethnic and geographic distribution, the highest reported among Ashkenazi Jews (30% in patients with familial PD, 14% in sporadic PD, 2.0% in controls) and North African Berbers (37% in patients with familial PD, 41% in sporadic PD, and 1% in controls). Little is known about the frequency of the LRRK2 p.G2019S among populations in sub-Saharan Africa. Our group and others previously reported that the p.G2019S is absent in a small cohort of Nigerian PD patients and controls. Here we used Kompetitive Allele Specific PCR (KASP) assay to screen for the p.G2019S in a larger cohort of Black African PD patients (n = 126) and healthy controls (n = 54) from Nigeria. Our analysis confirmed that all patients and controls are negative for the p.G2019S mutation. This report provides further evidence that the LRRK2 p.G2019S is not implicated in PD in black populations from Nigeria and support the notion that p.G2019S mutation originated after the early human dispersal from sub-Saharan Africa. Further studies using larger cohorts and advance sequencing technology are required to underpin the genetic causes of PD in this region.
截至目前，LRRK2 p.G2019S 突变仍然是全球最常见的帕金森病 (PD) 的遗传原因。它占家族性病例的 6%左右，散发性病例的 1.5%左右。LRRK2 具有激酶酶结构域，为药物治疗提供了有吸引力的潜在目标，并且正在开发 LRRK2 激酶抑制剂。p.G2019S 的患病率具有不同的种族和地理分布，在阿什肯纳兹犹太人中报道的最高（家族性 PD 患者中为 30%，散发性 PD 患者中为 14%，对照组中为 2.0%）和北非柏柏尔人（家族性 PD 患者中为 37%，散发性 PD 患者中为 41%，对照组中为 1%）。关于 p.G2019S 在撒哈拉以南非洲人群中的频率知之甚少。我们的研究小组和其他研究小组此前报告称，p.G2019S 在一小部分尼日利亚 PD 患者和对照组中不存在。在这里，我们使用 Kompetitive Allele Specific PCR (KASP) 检测方法在来自尼日利亚的更大的黑种人 PD 患者（n = 126）和健康对照组（n = 54）中筛查 p.G2019S。我们的分析证实，所有患者和对照组均为 p.G2019S 突变阴性。这一报告进一步证实了 LRRK2 p.G2019S 与尼日利亚黑人 PD 无关，并支持了 p.G2019S 突变起源于撒哈拉以南非洲早期人类扩散之后的观点。需要使用更大的队列和先进的测序技术进行进一步研究，以支持该地区 PD 的遗传原因。
