一氧化氮合酶1（NOS1）外显子18、一氧化氮合酶1外显子29、三磷酸腺苷结合盒转运蛋白B1（ABCB1）1236C/T及ABCB1 3435C/T基因多态性与帕金森病风险的遗传关联：一项荟萃分析。
Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease: A meta-analysis.
作者信息
Huang Hongbin, Peng Cong, Liu Yong, Liu Xu, Chen Qicong, Huang Zunnan
机构信息
Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan Scientific Research Center, Dongguan, Guangdong The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong Hunan key Laboratory of Skin Cancer and Psoriasis, The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, Zhanjiang, Guangdong Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, Guangxi, PR China.
出版信息
Medicine (Baltimore). 2016 Oct;95(40):e4982. doi: 10.1097/MD.0000000000004982.
BACKGROUND
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results.
METHODS
Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association.
RESULTS
The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09-1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32-2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26-2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02-1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66-0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03-1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility.
CONCLUSION
The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility.
背景
帕金森病（PD）是第二常见的神经退行性疾病。既往研究探讨了一氧化氮合酶1（NOS1）和ATP结合盒转运蛋白B1（ABCB1）基因多态性与帕金森病风险的关联。然而，这些研究得出了一些相互矛盾的结果。
方法
通过PubMed、Embase、PDgene、中国知网数据库和谷歌学术进行文献检索。应用比值比（OR）及95%置信区间（CI）评估关联强度。
结果
分析结果表明，NOS1基因第18外显子多态性在4种遗传模型中与帕金森病发病相关（等位基因：OR = 1.25，95%CI 1.09 - 1.44，P = 0.001；纯合子：OR = 1.79，95%CI 1.32 - 2.45，P < 0.001；隐性遗传：OR = 1.70，95%CI 1.26 - 2.28，P < 0.001；显性遗传：OR = 1.22，95%CI 1.02 - 1.46，P = 0.03），而第29外显子多态性与帕金森病易感性无关。此外，ABCB1基因1236C/T多态性在隐性遗传模型（OR = 0.80，95%CI 0.66 - 0.97，P = 0.025）和共显性模型（OR = 1.21，95%CI 1.03 - 1.43，P = 0.02）中与帕金森病相关，这可能表明该位点的2个小等位基因对帕金森病有相反的影响。然而，这一关联结果不够稳健，无法经受统计学显著性校正。另一方面，ABCB1基因3435C/T多态性在5种遗传模型中与帕金森病易感性均无关联，白种人和亚洲人的亚组分析进一步证实了这种无关联关系。无论这4个位点的多态性是否与帕金森病相关，我们的研究提供了一些有趣的发现，在遗传易感性方面与既往结果不同。
结论
NOS1基因第18外显子和ABCB1基因1236C/T变异可能在帕金森病风险中起作用，而NOS1基因第29外显子和ABCB1基因3435C/T多态性可能与帕金森病易感性无关。
Zotero 插件