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

Summary

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.

http://ift.tt/2y0aGHr