Abstract
Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.
Highlights
Leprosy is a chronic infectious disease which has affected mankind for more than 4,000 years[1]
The minor allele frequencies (MAF) of the SNPs analyzed in this study ranged from 5.8% to 48.4% (Table 1)
We found that presenilins-associated rhomboid-like (PARL) and PINK1 could physically interacted, co-expressed and genetically interacted with those proteins of the reported leprosy susceptibility genes, such as OPA1, PARK2, HLA-A, HLA-DRA, HLA-DQB, and IL10RA (Figure S5)
Summary
Leprosy is a chronic infectious disease which has affected mankind for more than 4,000 years[1]. When compared against its close relative, M. tuberculosis, the genome of M. leprae shows an extremely eroded evolution, which has led to nearly half of the functional genes (especially in the metabolic pathways) undergoing inactivation or pseudogenation[4,5,6]. This marked reduction in the number of working genes might be the primary reason why M. leprae has a long half-life in vivo and cannot be cultured in vitro. We provided solid evidence to show that the OPA1 gene, encoding an mitochondrial inner membrane protein, was associated with leprosy susceptibility possibly by affecting www.nature.com/scientificreports/. Mutations in PINK1 have been reported to be associated with Parkinson’s disease[28,33] and schizophrenia[34], but there was a controversy[27]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
