title: Mapping genetic variants in the CFH gene for association with leprosy in Han Chinese.
abstract: Complement factor H (CFH) is an essential regulator in the homeostasis of the complement system that plays multiple roles in leprosy. We previously reported a preliminary association of CFH with leprosy, but potentially causal variants remain to be identified. In this study, we performed a fine-mapping association analysis in 1110 individuals (527 leprosy patients and 583 controls) followed by bioinformatic analyses. We identified no association of typical missense CFH variants with leprosy and factor H-binding protein was not detected in Mycobacterium leprae. However, robust associations (PBonferroni<0.003) of several CFH intronic tag single-nucleotide polymorphisms with leprosy were observed. Expression quantitative trait locus analysis showed that these leprosy-protective alleles were associated with higher CFH level and lower CFHR3 (complement factor H-related 3) level. Our results indicated that CFH variants may contribute to leprosy pathogenesis through altering CFH expression, leading to regulation of complement activity rather than mediating immune evasion by bacteria binding.
authors.affiliation: 1] Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Yunnan, China [2] Kunming College of Life Sciences, University of Chinese Academy of Sciences, Yunnan, China.
authors.forename: D-F
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, Yunnan, China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Li
authors.affiliation: 1] Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Yunnan, China [2] Kunming College of Life Sciences, University of Chinese Academy of Sciences, Yunnan, China.
authors.forename: Y-G
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002681:China; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007918:Leprosy / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D009166:Mycobacterium leprae / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D000942:Antigens, Bacterial; D001798:Blood Proteins; C105970:CFHR3 protein, human; D017242:Complement Factor H