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- Title
A pleiotropic effect of the <italic>APOE</italic> gene: association of <italic>APOE</italic> polymorphisms with multibacillary leprosy in Han Chinese from Southwest China.
- Authors
Wang, D.; Zhang, D.‐F.; Li, G.‐D.; Bi, R.; Fan, Y.; Wu, Y.; Yu, X.‐F.; Long, H.; Li, Y.‐Y.; Yao, Y.‐G.
- Abstract
Summary: Background: Patients with leprosy have a very low risk of Alzheimer disease (AD) and β‐amyloid (Aβ) deposition is significantly lower in the brain tissue of elderly patients with leprosy compared with age‐matched controls. Apolipoprotein E (ApoE) plays a critical role in lipid metabolic pathways and in the brain, facilitating the proteolytic clearance of Aβ. We hypothesized that <italic>APOE</italic> confers risk of leprosy as lipid metabolism is involved in <italic>Mycobacterium leprae</italic> infection. Objectives: To investigate the potential genetic associations between <italic>APOE</italic> and leprosy in two independent Chinese case–control cohorts from the Yuxi and Wenshan prefectures, Yunnan Province of Southwest China. Methods: Five <italic>APOE</italic> single‐nucleotide polymorphisms (SNPs) were analysed in 1110 individuals (527 patients and 583 controls) from the Yuxi prefecture using a SNaPshot assay. Genetic variations in the entire <italic>APOE</italic> exons were screened in 1788 individuals (798 patients and 990 controls) from the Wenshan prefecture using next‐generation sequencing technology. Results: The AD‐associated SNPs rs405509 and rs439401 increased the risk of leprosy per se and multibacillary leprosy (<italic>P </italic><<italic> </italic>0·005), but the <italic>APOE</italic>‐ε4 allele did not. The SNPs rs405509 and rs439401 were <italic>cis</italic> expression quantitative trait loci (eQTL) for <italic>APOE</italic> expression in human skin. Differential <italic>APOE</italic> mRNA expression was observed in skin lesions of patients with type I reaction leprosy and those with multibacillary leprosy. <italic>APOE</italic> and related lipid genes are involved in an interaction network with leprosy susceptibility genes. Conclusions: The <italic>APOE</italic> gene is associated with leprosy, most likely by regulating lipid‐metabolism‐related genes.
- Subjects
HANSEN'S disease; ALZHEIMER'S disease; GENES; OLDER patients; METABOLISM
- Publication
British Journal of Dermatology, 2018, Vol 178, Issue 4, p931
- ISSN
0007-0963
- Publication type
Article
- DOI
10.1111/bjd.16020