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

BACKGROUND: Patients with leprosy have a very low risk of Alzheimer disease (AD) and ß-amyloid (Aß) 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 Aß. We hypothesized that APOE confers risk of leprosy as lipid metabolism is involved in Mycobacterium leprae infection. OBJECTIVES: 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 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 APOE 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 (P < 0·005), but the APOE-ε4 allele did not. The SNPs rs405509 and rs439401 were cis expression quantitative trait loci (eQTL) for APOE expression in human skin. Differential APOE mRNA expression was observed in skin lesions of patients with type I reaction leprosy and those with multibacillary leprosy. APOE and related lipid genes are involved in an interaction network with leprosy susceptibility genes. CONCLUSIONS: The APOE gene is associated with leprosy, most likely by regulating lipid-metabolism-related genes.

Alpha-1-antichymotrypsin is not associated with the increased frequency of apolipoprotein-E-epsilon-4 allele in elderly non-demented leprosy patients.

In our previous study, elderly leprosy patients showed a low prevalence of senile dementia of the Alzheimer type, but the frequency of apolipoprotein E (APO-E) epsilon 4 was elevated in non-demented elderly leprosy patients. Recent study has shown that Alzheimer's disease risk associated with APO-E epsilon 4 is significantly increased by the alpha 1-antichymotrypsin (ACT) genotype AA. Therefore we examined an association between ACT polymorphism and the APO-E epsilon 4 allele in 350 leprosy patients. None of our data showed an association of ACT genotype and APO-E epsilon 4 allele in leprosy patients. The allelic frequencies of the ACT gene did not differ even between demented patients with leprosy and age-matched controls. Our present data suggest that ACT polymorphism is not associated with the increased frequency of APO-E epsilon 4 in leprosy patients.