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Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China
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Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China
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Journal Article
Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China
2015
Overview
Leprosy is a chronic infectious and neurological disease that is caused by infection of
Mycobacterium leprae
(
M. leprae
). A recent genome-wide association study indicated a suggestive association of
LRRK2
genetic variant rs1873613 with leprosy in Chinese population. To validate this association and further identify potential causal variants of
LRRK2
with leprosy, we genotyped 13
LRRK2
variants in 548 leprosy patients and 1078 healthy individuals from Yunnan Province and (re-)analyzed 3225 Han Chinese across China. Variants rs1427267, rs3761863, rs1873613, rs732374 and rs7298930 were significantly associated with leprosy
per se
and/or paucibacillary leprosy (PB). Haplotype A-G-A-C-A was significantly associated with leprosy
per se
(
P
=0.018) and PB (
P
=0.020). Overexpression of the protective allele (Thr2397) of rs3761863 in HEK293 cells led to a significantly increased nuclear factor of activated T-cells’ activity compared with allele Met2397 after lipopolysaccharides stimulation. Allele Thr2397 could attenuate 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced autophagic activity in U251 cells. These data suggest that the protective effect of LRRK2 variant p.M2397T on leprosy might be mediated by increasing immune response and decreasing neurotoxicity after
M. leprae
loading. Our findings confirm that
LRRK2
is a susceptible gene to leprosy in Han Chinese population.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Alleles
/ Analysis
/ Asian Continental Ancestry Group - genetics
/ Biomedical and Life Sciences
/ Child
/ Female
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genomes
/ Humans
/ Leprosy
/ Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
/ Male
/ MPTP
/ Polymorphism, Single Nucleotide
