Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson's Disease in the Chinese Han Population
Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson's Disease in the Chinese Han Population
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中国汉族人群NGFR、ADAM17基因多态性与帕金森病的遗传关联
DOI：
10.1007/s12640-019-00031-z
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发表时间：
2019-10-01
影响因子：
3.7
通讯作者：
Wang, Yan-Jiang
中科院分区：
文献类型：
--
作者：
Li, Wei-Wei;Shen, Ying-Ying;Wang, Yan-Jiang
帕金森病是一种常见的以黑质神经元丢失为特征的神经退行性疾病。P75神经营养因子受体(p75NTR，NGFR编码)在黑质多巴胺神经元选择性死亡以及帕金森病的发生发展中起重要作用。为探讨神经生长因子受体基因多态性与帕金森病易感性的关系，对414例帕金森病患者和623例年龄、性别匹配的中国汉族人进行了病例对照研究。通过构建连锁不平衡块，从NGFR基因中筛选出12个标签单核苷酸多态(Tag-SNPs)。还选择了ADAM17基因中的一个Tag-SNP，因为它编码肿瘤坏死因子α转换酶，负责p75NTR胞外区的脱落。采用多重聚合酶链式反应-连接酶检测反应(PCR-LDR)进行基因分型。采用非条件Logistic回归分析Tag-SNPs与帕金森病发病风险的关系，采用共显性、显性、隐性、超显性、加性等5种遗传模型。结果表明，在13个Tag-SNPs中，rs741073与共显性(OR=0.71，95%CI=0.54~0.93，P=0.037)、显性(OR=0.76，95%CI=0.58~0.98，P=0.033)和过度显性模式(OR=0.71，95%CI=0.54~0.92，P=0.010)的帕金森病风险降低有关；显性(OR=0.69，95%CI=0.5~0.93，P=0.014)、超显性(OR=0.70，95%CI=0.5~0.96，P=0.025)和加性模型(OR=0.72，95%CI=0.54~0.94，P=0.016)。然而，在Bonferroni校正后，这些关联没有保留。总之，我们的研究未能揭示NGFR、ADAM17中选定的Tag-SNPs与帕金森病易感性之间的关联。P75NTR及其基因多态性在帕金森病发病机制中的作用有待进一步研究。
Parkinson's disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor alpha-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54-0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58-0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54-0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50-0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50-0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51-0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54-0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.