The mtDNA replication-related genes TFAM and POLG are associated with 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

	The mtDNA replication-related genes TFAM and POLG are associated with leprosy in Han Chinese from Southwest China
	Li GD 1,4; yaoyg@mail.kiz.ac.cn ; Rui B 4; Zhang DF 4; Long H 3; Li YY 2; Wang D 4; Fan Y 4; Yao YG*1,4; Yu XF 3
刊名	Journal of Dermatological Science
	2017
卷号	期号:页码:**
关键词	Leprosy Tfam Polg Eqtl Genetic Association Study
英文摘要	Background: The pathogen Mycobacterium leprae of leprosy is heavily dependent on the host energy metabolites and nutritional products for survival. Previously we and others have identified associations of several mitochondrion-related genes and mitochondrial DNA (mtDNA) copy number alterations with leprosy and/or its subtype. We hypothesized that genetic variants of mtDNA replication-related genes would affect leprosy. Objective:We aimed to identify genetic associations between the mtDNA replication-related genes TFAM, POLG and leprosy. Methods :Genetic association study was performed in 2898 individuals from two independent sample sets in Yunnan Province, China. We first screened 7 tag SNPs of TFAM and POLG in 527 leprosy cases and 583 controls (Sample I). Expression quantitative trait loci (eQTL) analysis and differential mRNA expression were analyzed to discern potential effect of risk variants. The entire exon region of TFAM and POLG were further analyzed in 798 leprosy cases and 990 controls (Sample II, 4327 East Asians from the ExAC dataset was included as a reference control) by using targeted gene sequencing for fine mapping potentially causal variants. Results: Two tag SNPs of TFAM (rs1049432, P = 0.007) and POLG (rs3176238, P = 0.006) were associated with multibacillary leprosy (MB) in Sample I and the significance survived correction for multiple comparisons. SNPs rs1937 of TFAM (which was linked with rs1049432) and rs61756401 of POLG were associated with leprosy, whereas no potentially causative coding variants were identified in Sample II. The eQTL analysis showed that rs1049432 was a significant cis eQTL for TFAM in nerve tissue (P = 1.2010 -12 ), and rs3176238 was a significant cis eQTL for POLG in nerve (P = 3.9010 -13 ) and skin tissues (P = 2.5010 -11 ). Consistently, mRNA level of POLG was differentially expressed in leprotic skin lesions. Conclusions: Genetic variants of TFAM and POLG were associated with leprosy in Han Chinese, presumably by affecting gene expression.
语种	英语
资助机构	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 ; 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 ; 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 ; 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/152453/12043]
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
作者单位	1.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650201, China 2.epartment of Dermatology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China 3.Wenshan Institute of Dermatology, Wenshan, Yunnan, 663000, China 4.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
推荐引用方式 GB/T 7714	Li GD,yaoyg@mail.kiz.ac.cn,Rui B,et al. The mtDNA replication-related genes TFAM and POLG are associated with leprosy in Han Chinese from Southwest China[J]. Journal of Dermatological Science,2017,():**.
APA	Li GD.,yaoyg@mail.kiz.ac.cn.,Rui B.,Zhang DF.,Long H.,...&Yu XF.(2017).The mtDNA replication-related genes TFAM and POLG are associated with leprosy in Han Chinese from Southwest China.Journal of Dermatological Science,(),**.
MLA	Li GD,et al."The mtDNA replication-related genes TFAM and POLG are associated with leprosy in Han Chinese from Southwest China".Journal of Dermatological Science .(2017):**.