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Genetic variants of complement genes Ficolin-2, Mannose-binding lectin and Complement factor H are associated with leprosy in Han Chinese from Southwest China

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Abstract

The complement system plays multiple roles in host defense against infection and is supposed to confer genetic susceptibility to leprosy. We aimed to examine whether genetic variants of the Ficolin-2 (FCN2), Mannose-binding lectin (MBL2) and Complement factor H (CFH) genes, which are involved in activation and regulation of the complement system, are associated with leprosy in Han Chinese from Southwest China. 527 leprosy patients and 583 matched controls were recruited from Yunnan Province, China, and were analyzed in this study. We sequenced the promoter region of the FCN2 and MBL2 genes and exon 8 of the FCN2 gene and genotyped three tag SNPs of the CFH gene. Association analysis was performed to discern potential effect of these three genes with leprosy and its subtypes. Luciferase assay was used to characterize the role of different promoter alleles of the FCN2 and MBL2 genes. Genetic variants of FCN2 (rs3811140 and rs7851696), MBL2 (rs11003125, rs7100749, rs11003124 and rs7096206) and CFH (rs1065489 and rs3753395) were significantly associated with leprosy and its subtypes. Haplotypes/genotypes representing low FCN2 and MBL2 transcriptional activity conferred risk to paucibacillary leprosy. Our data confirmed the expected positive association of complement genes with leprosy susceptibility and clinical outcomes in Han Chinese.

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Acknowledgments

We thank all the participants in this study and Mr. Mei-Sheng Xiao and Miss Ling Xu for assistance with luciferase assay. This study was supported by the National Natural Science Foundation of China (31271346, 30925021 and 81260237), Top Talents Program of Yunnan Province (2009CI119) and the Chinese Academy of Sciences.

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All authors declare no potential conflicts.

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Authors and Affiliations

  1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China

    Deng-Feng Zhang, Dong Wang & Yong-Gang Yao

  2. Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China

    Xian-Qiong Huang & Yu-Ye Li

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Deng-Feng Zhang & Dong Wang

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  1. Deng-Feng Zhang
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  2. Xian-Qiong Huang
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Correspondence to Yong-Gang Yao.

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Zhang, DF., Huang, XQ., Wang, D. et al. Genetic variants of complement genes Ficolin-2, Mannose-binding lectin and Complement factor H are associated with leprosy in Han Chinese from Southwest China. Hum Genet 132, 629–640 (2013). https://doi.org/10.1007/s00439-013-1273-8

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