Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Hum Genet. 2011 Jun;129(6):611-5. doi: 10.1007/s00439-011-0955-3. Epub 2011 Feb 2.
LINGO2, a member of LRR gene family, has been linked with both Essential tremor (ET) and Parkinson's disease (PD). However, there is a lack of conclusive evidence regarding the etiologic role of LINGO2 genetic variants. We investigated the association of LINGO2 variants with ET and PD in two independent Asian countries. A total of 1,262 subjects comprising 499 controls, 436 PD patients, and 327 ET patients were included. Eight LINGO2 variants, including four single-nucleotide polymorphisms (SNPs) and four coding variants, were initially analyzed in one Asian population. SNPs that showed positive association were then replicated in the second independent Asian population, and a pooled analysis was carried out. Out of the eight variants, two SNPs (rs7033345 and rs10812774) revealed significant or strong positive trend in the first Asian population, and these were analyzed in the second Asian population. In the pooled analysis, the CC genotype at rs7033345 had a higher risk of developing PD (OR = 1.67, 95% CI = 1.18, 2.35, p = 0.003) and ET (OR = 1.50, 95% CI = 1.02, 2.20, p = 0.04) under a recessive model. The C allele at rs10812774 increased the risk of ET (OR = 1.56 95% CI = 1.10, 2.22, p = 0.01) via a recessive model. The effect size and direction of trend were in the same direction in each of the two populations. Our study demonstrated for the first time that rs7033345 is associated with PD and ET and rs10812774 with ET among Asians, suggesting that LINGO2 might act as a susceptibility gene for both conditions.
LRR 基因家族的成员 LINGO2 与特发性震颤（ET）和帕金森病（PD）均有关联。然而，关于 LINGO2 遗传变异的病因作用尚缺乏确凿的证据。我们在两个独立的亚洲国家研究了 LINGO2 变异与 ET 和 PD 的相关性。共纳入 1262 名受试者，包括 499 名对照、436 名 PD 患者和 327 名 ET 患者。我们最初在一个亚洲人群中分析了 8 种 LINGO2 变异，包括 4 种单核苷酸多态性（SNP）和 4 种编码变异。在第二个独立的亚洲人群中对表现出阳性关联的 SNP 进行了复制，并进行了合并分析。在这 8 个变体中，有两个 SNP（rs7033345 和 rs10812774）在第一个亚洲人群中显示出显著或强烈的阳性趋势，并且在第二个亚洲人群中进行了分析。在合并分析中，rs7033345 的 CC 基因型患 PD（OR=1.67，95%CI=1.18，2.35，p=0.003）和 ET（OR=1.50，95%CI=1.02，2.20，p=0.04）的风险更高，采用的是隐性模型。rs10812774 的 C 等位基因通过隐性模型增加了患 ET（OR=1.56，95%CI=1.10，2.22，p=0.01）的风险。在两个人群中，每个人群的效应大小和趋势方向均一致。我们的研究首次表明，rs7033345 与 PD 和 ET 相关，rs10812774 与 ET 相关，这表明 LINGO2 可能是这两种疾病的易感基因。
