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Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China

Abstract

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.

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Acknowledgements

We are grateful to all the participants in this study. We thank Mr Jia-Qi Feng and Dr Yue-Mei Feng for technical assistance. This study was supported by the National Natural Science Foundation of China (31271346 and 30925021) and the Ministry of Science and Technology of China (2011CB910902). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Correspondence to Y-G Yao.

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Wang, D., Xu, L., Lv, L. et al. Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China. Genes Immun 16, 112–119 (2015). https://doi.org/10.1038/gene.2014.72

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