Lin C H, Tan E K, Chen M L, Tan L C, Lim H Q, Chen G S, Wu R M
Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Neurology. 2008 Nov 18;71(21):1727-32. doi: 10.1212/01.wnl.0000335167.72412.68.
To assess the association of ATP13A2 gene mutation among patients with early onset Parkinson disease (EOPD, onset < 50 years) in ethnic Chinese population.
Among 771 subjects, we studied 182 patients with EOPD and familial PD and 589 matched controls from two cohorts of Han Chinese in Taiwan and Singapore. The entire ATP13A2 coding region and intron-exon boundaries were sequenced in 71 probands and 70 controls in Taiwanese/ethnic Chinese. An additional 111 index patients with PD in Singapore and 589 controls were later screened to validate possible mutations that were found in the first set of study subjects.
We identified one novel missense variant, AL746Thr, in a single heterozygous state in three patients (two were from Taiwan and one was from Singapore) (1.7% in EOPD). The variant was not observed in 589 ethnicity matched controls. The frequency of this variant was significantly higher in PD cases than controls (p = 0.01, relative risk 4.3, 95% CI 1.9-4.3). The clinical phenotype and (18)F-dopa PET image of ATP13A2 Ala78Thr carriers are similar to that seen in idiopathic PD. The variant is located between the highly conserved phosphorylation region and the fifth transmembrane domain of the ATP13A2 protein.
A rare variant of the ATP13A2 was associated with an increased risk of Parkinson disease among ethnic Chinese in Asia. Further studies are needed to clarify the functional role of this genetic risk factor.
评估中国汉族人群中早发性帕金森病（EOPD，发病年龄<50岁）患者中ATP13A2基因突变的相关性。
在771名受试者中，我们研究了来自台湾和新加坡的两个汉族队列中的182例EOPD和家族性帕金森病患者以及589名匹配的对照。对71名台湾汉族/华裔先证者和70名对照的整个ATP13A2编码区及内含子-外显子边界进行了测序。随后对新加坡的另外111例帕金森病索引患者和589名对照进行筛查，以验证在第一组研究对象中发现的可能突变。
我们在三名患者（两名来自台湾，一名来自新加坡）中发现了一种新的错义变异，即杂合状态的AL746Thr（在EOPD中占1.7%）。在589名种族匹配的对照中未观察到该变异。该变异在帕金森病患者中的频率显著高于对照（p = 0.01，相对风险4.3，95%可信区间1.9 - 4.3）。ATP13A2 Ala78Thr携带者的临床表型和（18）F - 多巴PET图像与特发性帕金森病相似。该变异位于ATP13A2蛋白高度保守的磷酸化区域和第五个跨膜结构域之间。
ATP13A2的一种罕见变异与亚洲华裔人群帕金森病风险增加相关。需要进一步研究以阐明这种遗传风险因素的功能作用。
