A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室

	A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China
	Yao YG1,3; yaoyg@mail.kiz.ac.cn ; Li GD 1,3; wangdong@mail.kiz.ac.cn ; Wang D1; Bi R 1; Fan Y 1; Yu XF 2; Long H 2; Zhang DF 1
刊名	British Jouranl Dermatology
	2018
卷号	期号:页码:Epub ahead of print
关键词	Apoe Alzheimer's Disease Genetic Susceptibility Leprosy Lipid
英文摘要	BACKGROUND: Leprosy patients had a very low risk of Alzheimer's disease (AD), and the β-amyloid (Aβ) deposition was significantly lower in the brain tissues of elderly leprosy patients than those of age-matched controls. The APOE played critical roles in lipid metabolic pathways and in brain to facilitate the proteolytic clearance of Aβ. We hypothesized that APOE would confer risk to leprosy as lipid metabolism was involved in Mycobacterium leprae infection. OBJECTIVE: To investigate the potential genetic associations between APOE and leprosy in two independent Chinese case-control cohorts from the Yuxi and Wenshan Prefectures, Yunnan Province of Southwest China. METHODS: Five APOE SNPs were analyzed in 1110 individuals (527 patients and 583 controls) from the Yuxi Prefecture by using SNaPshot assay. Genetic variations in the entire APOE exons of were screened in 1788 individuals (798 patients and 990 controls) from the Wenshan Prefecture by using the next generation sequencing technology. RESULTS: The AD-associated SNPs rs405509 and rs439401 increased risk to leprosy per se and multibacillary leprosy (MB, P < 0.005), but APOE-ε4 allele did not affect leprosy. SNPs rs405509 and rs439401 were cis eQTLs for APOE expression in human skin. Differential APOE mRNA expression was observed in skin lesions of type I reaction leprosy and MB patients. The APOE and related lipid genes were participated in a highly interacted network with leprosy susceptibility genes. CONCLUSIONS: The APOE gene was associated with leprosy, most likely by regulating lipid metabolism related genes. This article is protected by copyright. All rights reserved.
语种	英语
资助机构	ted Article This article is protected by copyright. All rights reserved. putative interaction of APOE and MBL2: the plasma Apoe and Mbl2 levels were correlated with diabetic phenotype in New Zealand obese mice 60 , and APOE and MBL genotypes were associated with increased risk of neurocognitive impairment in HIV-infected donors 61 . Similarly, we found a higher mRNA expression level of MBL2 in skin lesion of MB patients relative to control tissues (Table S6). Therefore, the information provided by network analysis might direct future functional experiments to elucidate its potential biological significance in leprosy. In short, we found that APOE SNPs rs405509 and rs439401 were associated with leprosy, and the effect might be mediated by altered APOE mRNA expression and its potential role in lipid metabolic pathways during M. leprae infection. Future studies are needed to validate our current observation and to explore potential function of APOE during leprosy onset and progression. Acknowledgement This study was supported by the National Natural Science Foundation of China (81573034, 31271346), Yunnan Province (2014FB177) and West Light Foundation of the Chinese Academy of Sciences. ; ted Article This article is protected by copyright. All rights reserved. putative interaction of APOE and MBL2: the plasma Apoe and Mbl2 levels were correlated with diabetic phenotype in New Zealand obese mice 60 , and APOE and MBL genotypes were associated with increased risk of neurocognitive impairment in HIV-infected donors 61 . Similarly, we found a higher mRNA expression level of MBL2 in skin lesion of MB patients relative to control tissues (Table S6). Therefore, the information provided by network analysis might direct future functional experiments to elucidate its potential biological significance in leprosy. In short, we found that APOE SNPs rs405509 and rs439401 were associated with leprosy, and the effect might be mediated by altered APOE mRNA expression and its potential role in lipid metabolic pathways during M. leprae infection. Future studies are needed to validate our current observation and to explore potential function of APOE during leprosy onset and progression. Acknowledgement This study was supported by the National Natural Science Foundation of China (81573034, 31271346), Yunnan Province (2014FB177) and West Light Foundation of the Chinese Academy of Sciences. ; ted Article This article is protected by copyright. All rights reserved. putative interaction of APOE and MBL2: the plasma Apoe and Mbl2 levels were correlated with diabetic phenotype in New Zealand obese mice 60 , and APOE and MBL genotypes were associated with increased risk of neurocognitive impairment in HIV-infected donors 61 . Similarly, we found a higher mRNA expression level of MBL2 in skin lesion of MB patients relative to control tissues (Table S6). Therefore, the information provided by network analysis might direct future functional experiments to elucidate its potential biological significance in leprosy. In short, we found that APOE SNPs rs405509 and rs439401 were associated with leprosy, and the effect might be mediated by altered APOE mRNA expression and its potential role in lipid metabolic pathways during M. leprae infection. Future studies are needed to validate our current observation and to explore potential function of APOE during leprosy onset and progression. Acknowledgement This study was supported by the National Natural Science Foundation of China (81573034, 31271346), Yunnan Province (2014FB177) and West Light Foundation of the Chinese Academy of Sciences. ; ted Article This article is protected by copyright. All rights reserved. putative interaction of APOE and MBL2: the plasma Apoe and Mbl2 levels were correlated with diabetic phenotype in New Zealand obese mice 60 , and APOE and MBL genotypes were associated with increased risk of neurocognitive impairment in HIV-infected donors 61 . Similarly, we found a higher mRNA expression level of MBL2 in skin lesion of MB patients relative to control tissues (Table S6). Therefore, the information provided by network analysis might direct future functional experiments to elucidate its potential biological significance in leprosy. In short, we found that APOE SNPs rs405509 and rs439401 were associated with leprosy, and the effect might be mediated by altered APOE mRNA expression and its potential role in lipid metabolic pathways during M. leprae infection. Future studies are needed to validate our current observation and to explore potential function of APOE during leprosy onset and progression. Acknowledgement This study was supported by the National Natural Science Foundation of China (81573034, 31271346), Yunnan Province (2014FB177) and West Light Foundation of the Chinese Academy of Sciences.
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/12044]
专题	昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_重大疾病机理的遗传学
通讯作者	yaoyg@mail.kiz.ac.cn; wangdong@mail.kiz.ac.cn
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China 2.Wenshan Institute of Dermatology, Wenshan, Yunnan, 663000, China 3.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650201, China 4.Department of Dermatology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China
推荐引用方式 GB/T 7714	Yao YG,yaoyg@mail.kiz.ac.cn,Li GD,et al. A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China[J]. British Jouranl Dermatology,2018,(*):Epub ahead of print.
APA	Yao YG.,yaoyg@mail.kiz.ac.cn.,Li GD.,wangdong@mail.kiz.ac.cn.,Wang D.,...&Li YY.(2018).A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China.British Jouranl Dermatology,(),Epub ahead of print.
MLA	Yao YG,et al."A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China".British Jouranl Dermatology .*(2018):Epub ahead of print.