Ji Wenzhen, Zhang Yu
Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin 300000, China.
Division of Medical Affairs, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin 300000, China.
Oncotarget. 2017 Nov 6;8(64):107870-107876. doi: 10.18632/oncotarget.22330. eCollection 2017 Dec 8.
The objective of this study was to explore the genetic association of myeloperoxidase () gene polymorphisms with risk of Alzheimer's disease (AD).
Blood samples were collected from 116 AD patients and 134 age and gender matched healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to confirm polymorphisms in promoter region. Plasma concentration of MPO was detected by enzyme-linked immuno sorbent assay. Genotype distributions of polymorphisms were compared by χ test between the two groups. The status of linkage disequilibrium between two polymorphisms was detected using Haploview. MPO concentrations were analyzed by non-parametric test.
rs2333227 polymorphism was positively associated with AD risk, especially under the AA+GA vs. GG and A vs. G genetic models (=0.042, OR=1.719, 95%CI=1.017-2.906; =0.041, OR=1.582, 95%CI=1.016-2.463). While, rs34097845 polymorphism significantly decreased the risk of AD, particularly GA and AA+GA genotypes (=0.048, OR=0.555, 95%CI=0.308-0.998; =0.042, OR=0.552, 95%CI=0.310-0.983). In addition, rs2333227 genotypes affected the plasma concentration of MPO. But for rs34097845 polymorphism, only GA genotype exhibited significant association with MPO concentration.
Polymorphisms in the promoter region of distinctly contribute to AD risk possibly through regulating MPO concentration. Present results should be confirmed by further studies.
本研究旨在探讨髓过氧化物酶（MPO）基因多态性与阿尔茨海默病（AD）风险的遗传关联。
采集116例AD患者及134例年龄和性别匹配的健康个体的血样。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法确定启动子区域的MPO多态性。采用酶联免疫吸附测定法检测血浆MPO浓度。通过χ²检验比较两组间MPO多态性的基因型分布。使用Haploview检测两个多态性之间的连锁不平衡状态。采用非参数检验分析MPO浓度。
rs2333227多态性与AD风险呈正相关，尤其是在AA+GA与GG以及A与G遗传模型下（P=0.042，OR=1.719，95%CI=1.017-2.906；P=0.041，OR=1.582，95%CI=1.016-2.463）。而rs34097845多态性显著降低AD风险，特别是GA和AA+GA基因型（P=0.048，OR=0.555，95%CI=0.308-0.998；P=0.042，OR=0.552，95%CI=0.310-0.983）。此外，rs2333227基因型影响血浆MPO浓度。但对于rs34097845多态性，仅GA基因型与MPO浓度呈显著相关。
MPO启动子区域的多态性可能通过调节MPO浓度显著影响AD风险。目前的结果有待进一步研究证实。
