LRRK2 P755L variant in sporadic Parkinson's disease
LRRK2 P755L variant in sporadic Parkinson's disease
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DOI：
10.1007/s10038-008-0336-5
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发表时间：
2008-10
影响因子：
3.5
通讯作者：
H. Tomiyama;I. Mizuta;Yuanzhe Li;M. Funayama;H. Yoshino;Lin Li;M. Murata;Mitsutoshi Yamamoto;S. Kubo;Y. Mizuno;T. Toda;N. Hattori
中科院分区：
文献类型：
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作者：
H. Tomiyama;I. Mizuta;Yuanzhe Li;M. Funayama;H. Yoshino;Lin Li;M. Murata;Mitsutoshi Yamamoto;S. Kubo;Y. Mizuno;T. Toda;N. Hattori
帕金森病（PD）是一种病因不明的神经退行性疾病，可能与遗传环境因素有关。大多数PD病例（约90-95%）是散发的，而家族性病例约占PD的5-10%。在最近的一份报告中，在2%的中国散发性PD患者和0%的正常对照或白种人中发现了LRRK2 P755L杂合突变，这表明该突变与疾病的种族特异性有关。为了进一步评估LRRK2 P755L变异在散发性PD中的作用，我们对501名日本散发性PD患者（男性249名，女性252名，年龄28-92岁，平均65.0岁）和583名日本普通人群的对照进行了LRRK2外显子19的直接测序，作为一项扩展关联研究。本组共发现6例患者（6/501= 1.2%）和8例对照组（8/583= 1.6%）携带P755L杂合变异（P= 0.80, χ 2= 0.064）。外显子19未发现其他变异。结合先前的报道，我们的大样本量的扩展病例对照研究表明，LRRK2 P755L在PD患者中是一种与疾病无关的多态性。
Parkinson’s disease (PD) is a neurodegenerative disorder of unknown etiology with probable involvement of genetic-environmental factors. The majority of PD cases (approximately 90–95%) are sporadic, while familial cases account for approximately 5–10% of PD. In a recent report, a heterozygous LRRK2 P755L mutation within LRRK2 exon 19 was found in 2% of Chinese sporadic PD patients and in 0% of normal controls or Caucasians, suggesting that the mutation is disease-associated with ethnic specificity. To further evaluate the role of LRRK2 P755L variant in sporadic PD, we performed direct sequencing of LRRK2 exon 19 in 501 Japanese sporadic PD patients (male 249, female 252, aged 28–92 years, mean 65.0 years) and 583 controls of the Japanese general population as an extended association study. In this group, we found six patients (6/501= 1.2%) and eight controls of the general population (8/583= 1.6%) with a heterozygous P755L variant (P= 0.80, χ 2= 0.064). No other variants were found in exon 19. Together with previous reports, our extended case-controlled study of large sample size suggests that LRRK2 P755L is a non-disease-associated polymorphism in PD patients.