Epidemiology Research and Methods LLC, Atlanta, GA, USA.
Biogen, Cambridge, MA, USA.
Parkinsonism Relat Disord. 2022 May;98:103-113. doi: 10.1016/j.parkreldis.2022.05.012. Epub 2022 May 25.
Variants in the leucine-rich repeat kinase 2 gene (LRRK2) are risk factors for Parkinson's disease (PD), but their prevalence varies geographically, reflecting the locations of founder events and dispersion of founders' descendants.
A comprehensive literature review was conducted to identify studies providing prevalence estimates for any of ten variants in LRRK2 (G2019S, R1441C, R1441G, R1441H, I2020T, N1437H, Y1699C, S1761R, G2385R, R1628P) among individuals with PD globally. We calculated crude country-specific variant prevalence estimates and, when possible, adjusted estimates for ethno-racial composition. For clinic-based studies, probands were used over other familial cases, whereas for population-based studies, all PD cases were used.
The analysis included 161 articles from 52 countries yielding 581 prevalence estimates across the ten variants. G2019S was the most common variant, exceeding 1.0% in 26 of 51 countries with estimates. The other variants were far less common. G2385R and R1628P were observed almost exclusively in East Asian countries, where they were found in ∼5-10% of cases. All prevalence estimates adjusted for ethno-racial composition were lower than their unadjusted counterparts, although data permitting this adjustment was only available for six countries.
Except for G2019S, the LRRK2 variants covered in this review were uncommon in most countries studied. However, there were countries with higher prevalence for some variants, reflecting the uneven geographic distribution of LRRK2 variants. The fact that ethno-racial group‒adjusted estimates were lower than crude estimates suggests that estimates derived largely from clinic-based studies may overstate the true prevalence of some LRRK2 variants in PD.
富含亮氨酸重复激酶 2 基因 (LRRK2) 的变异是帕金森病 (PD) 的风险因素，但它们的流行率在地理上有所不同，反映了创始事件的位置和创始人家族后裔的分布情况。
我们进行了全面的文献综述，以确定提供全球 PD 患者中 LRRK2 十种变异（G2019S、R1441C、R1441G、R1441H、I2020T、N1437H、Y1699C、S1761R、G2385R、R1628P）流行率估计值的研究。我们计算了各国未经调整的变异流行率估计值，并在可能的情况下，根据种族构成进行了调整。对于基于诊所的研究，使用先证者而不是其他家族病例，而对于基于人群的研究，则使用所有 PD 病例。
分析包括来自 52 个国家的 161 篇文章，涵盖了这十种变异的 581 个流行率估计值。G2019S 是最常见的变异，在 51 个有估计值的国家中的 26 个国家中超过 1.0%。其他变异则较为少见。G2385R 和 R1628P 几乎只在东亚国家中发现，其在这些国家的病例中约占 5-10%。在调整了种族构成的情况下，所有流行率估计值都低于未经调整的估计值，尽管只有六个国家有允许进行这种调整的数据。
除了 G2019S 以外，本综述涵盖的 LRRK2 变异在大多数研究的国家中并不常见。然而，有些国家的某些变异的流行率较高，反映了 LRRK2 变异在地理上的不均匀分布。基于诊所的研究可能会高估某些 LRRK2 变异在 PD 中的真实流行率，这一事实表明，经过种族构成调整的估计值低于未经调整的估计值。
