Calbindin 1, fibroblast growth factor 20, and α-synuclein in sporadic Parkinson's disease
Calbindin 1, fibroblast growth factor 20, and α-synuclein in sporadic Parkinson's disease
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DOI：
10.1007/s00439-008-0525-5
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发表时间：
2008-08-01
期刊：
影响因子：
5.3
通讯作者：
Toda, Tatsushi
中科院分区：
文献类型：
--
作者：
Mizuta, Ikuko;Tsunoda, Tatsuhiko;Toda, Tatsushi
帕金森病（PD）是人类最常见的神经退行性疾病之一，其特征是中脑黑质中多巴胺能神经元的丧失。我们最近对121个候选基因中的268个snp进行了病例对照关联研究，发现α -突触核蛋白（SNCA）是散发性PD的易感基因（P = 1.7 x 10(-11)）。我们还重复了成纤维细胞生长因子20 （FGF20）与PD的关联（P = 0.0089）。为了寻找其他的易感基因，我们在之前的筛选中增加了34个snp。在137个基因的302个snp中，除SNCA外，NDUFV2、FGF2、CALB1和B2M的snp均有显著相关性（P < 0.01； 882例，938例对照）。我们在第二个独立样本集（521例和1003例对照）中重复了这些snp的关联分析。calbindin 1 （CALB1）中的rs1805874 SNP在两种分析中均显示出显著性(P = 7.1 × 10(-5)；隐性模型)。当对SNCA基因型进行分层分析时，CALB1的优势比有随SNCA中保护性等位基因数量增加而增加的趋势。相比之下，FGF20仅在SNCA风险等位基因纯合子亚组中具有显著性。CALB1是一种钙结合蛋白，在神经元中广泛表达。的相对节省
Parkinson's disease (PD), one of the most common human neurodegenerative disorders, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. Our recent case- control association study of 268 SNPs in 121 candidate genes identified alpha-synuclein ( SNCA) as a susceptibility gene for sporadic PD (P = 1.7 x 10(-11)). We also replicated the association of fibroblast growth factor 20 ( FGF20) with PD ( P = 0.0089). To find other susceptibility genes, we added 34 SNPs to the previous screen. Of 302 SNPs in a total 137 genes, but excluding SNCA, SNPs in NDUFV2, FGF2, CALB1 and B2M showed significant association ( P < 0.01; 882 cases and 938 control subjects). We replicated the association analysis for these SNPs in a second independent sample set ( 521 cases and 1,003 control subjects). One SNP, rs1805874 in calbindin 1 ( CALB1), showed significance in both analyses ( P = 7.1 x 10(-5); recessive model). When the analysis was stratified relative to the SNCA genotype, the odds ratio of CALB1 tended to increase according to the number of protective alleles in SNCA. In contrast, FGF20 was significant only in the subgroup of SNCA homozygote of risk allele. CALB1 is a calcium-binding protein that widely is expressed in neurons. A relative sparing of