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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 ( P   adjusted   = 0.019) and multibacillary leprosy (MB,  P   adjusted   = 0.020) at the allelic level. rs12631031 and rs7653061 in  PARL  were associated with leprosy and MB (dominant model,  P   adjusted   < 0.05) at the genotypic level.  PINK1  SNP rs4704 was associated with leprosy at the genotypic level ( P   adjusted   = 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.

Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China