Chao Yin Xia, Ng Ebonne Yulin, Tan Louis, Prakash Kumar M, Au Wing-Lok, Zhao Yi, Tan Eng-King
1] Departments of Neurology, Singapore General Hospital [2] National Neuroscience Institute.
National Neuroscience Institute.
Sci Rep. 2015 Mar 12;5:9029. doi: 10.1038/srep09029.
Essential tremor (ET) and Parkinson's disease (PD) are two of the most common adult onset movement disorders with overlapping clinical features. PD patients with leucine-rich repeat kinase-2 (LRRK2) mutations may present initially with an ET phenotype. To address the possibility of a common genetic link between ET and PD, we examined the association between a common LRRK2 R1628P gene variant and ET. The LRRK2 R1628P was genotyped in ET cases and matched healthy controls. A total of 1277 subjects comprising of 450 ET cases and 827 controls were included. There were 40 heterozygote (GG to CG) variant out of 450 ET cases (genotypic frequency 8.9%) and 36 heterozygote variant (GG to CG, genotypic frequency 4.3%) and one homozygote variant (GG to CC) out of 827 controls. Subjects carrying the R1628P variant had a twofold increased risk of ET (p = 0.0035, OR = 2.20 and 95% confidence interval is 1.30-3.73). Using a case control methodology, we demonstrated an association between a known PD risk variant, LRRK2 R1628P, with ET. Subjects carrying the R1628P variant had twice the risk of developing ET. The sharing of a similar gene risk variant suggests a possible pathophysiologic link between PD and ET.
特发性震颤（ET）和帕金森病（PD）是两种最常见的成年起病的运动障碍，具有重叠的临床特征。携带富含亮氨酸重复激酶2（LRRK2）突变的PD患者最初可能表现为ET表型。为了探讨ET和PD之间存在共同遗传联系的可能性，我们研究了常见的LRRK2 R1628P基因变异与ET之间的关联。对ET患者和匹配的健康对照进行LRRK2 R1628P基因分型。共纳入1277名受试者，包括450例ET患者和827名对照。450例ET患者中有40例杂合子（GG到CG）变异（基因型频率8.9%），827名对照中有36例杂合子变异（GG到CG，基因型频率4.3%）和1例纯合子变异（GG到CC）。携带R1628P变异的受试者患ET的风险增加两倍（p = 0.0035，OR = 2.20，95%置信区间为1.30 - 3.73）。通过病例对照研究方法，我们证明了已知的PD风险变异LRRK2 R1628P与ET之间存在关联。携带R1628P变异的受试者患ET的风险是正常人的两倍。共享相似的基因风险变异提示PD和ET之间可能存在病理生理联系。
