title: Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China.
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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.|Department of Dermatology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Feng
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Li
authors.affiliation: Yuxi City Center for Disease Control and Prevention, Yuxi, Yunnan, 653100, China.
authors.forename: Xiao-An
authors.initials: XA
authors.lastname: Li
authors.affiliation: Wenshan Institute of Dermatology, Wenshan, Yunnan, 663000, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Yu
authors.affiliation: Wenshan Institute of Dermatology, Wenshan, Yunnan, 663000, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Long
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
authors.forename: Yu-Ye
authors.initials: YY
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007918:Leprosy / Q000235:genetics*; D008297:Male; D045726:Metalloproteases / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult; D000099202:PTEN-Induced Putative Kinase
chemical_list: D045726:Metalloproteases; D024101:Mitochondrial Proteins; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C485223:PARL protein, human