Genetic variants of SNCA and LRRK2 genes are associated with sporadic PD susceptibility: A replication study in a Taiwanese cohort

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• 作者：Yah-Huei Wu-Chou^a ; ^b ; Ying-Ting Chen^c ; Tu-Hsueh Yeh^b ; ^d ; Hsiu-Chen Chang^d ; Yi-Hsin Weng^b ; ^d ; Szu-Chia Lai^b ; ^d ; Chia-Ling Huang^e ; Rou-Shayn Chen^b ; ^d ; Ying-Zu Huang^b ; ^d ; Chiung-Chu Chen^b ; ^d ; June Hung^d ; Wen-Li Chuang^d ; Wey-Yil Lin^d ; Chien-Hsiun Chen^c ; Chin-Song Lu^b ; ^d ; ^{c81214@adm.cgmh.org.tw}
• 关键词：Genetic susceptibility ; SNCA ; LRRK2 ; Replication study ; Parkinson's disease
• 刊名：Parkinsonism and Related Disorders
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：19
• 期：2
• 页码：251-255
• 全文大小：246 K

文摘

Background

Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative diseases and usually refers to a complex disorder with multiple genetic and environmental factors influencing disease risk. We here performed a gene-based case-control association study to scrutinize whether genetic variants in SNCA and LRRK2 genes could predispose to sporadic, late-onset form of PD in Taiwanese population.

Methods

17 Single Nucleotide Polymorphisms (SNPs) markers located within SNCA gene as well as the 16 SNP markers within LRRK2 gene were chosen for genotyping and evaluated their haplotype structure in a cohort of sporadic PD patients and control individuals.

Results

This study showed that two SNPs near the promoter region (rs2301134 and rs2301135) of SNCA gene gave the greatest evidence for an association with PD (p?¡Ü?0.01) and a haplotype block with two SNPs in the 3¡ä UTR (rs356221 and rs11931074) revealed another evidence of association (p?¡Ü?0.02). For the LRRK2 gene, only R1628P variants of total 16 SNPs giving a marginal significant association with PD across the whole gene (p?=?0.0058) and no haplotype block was constructed. Many genetic variants (A419V, I1122V, R1441C, R1441G, R1441H, Y1699C, M1869 V, M1869T, I2012T, G2019S, and I2020T) from previous reports were not detected in our cohort.

Conclusions

We have replicated a population-based PD association study in a collection of 626 cases and 473 control subjects and confirm that genetic variants of both SNCA and LRRK2 genes are associated with susceptibility to sporadic PD but in a different distribution.