Mapping genetic variants in the CFH gene for association with leprosy in Han Chinese
Mapping genetic variants in the CFH gene for association with leprosy in Han Chinese
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DOI：
10.1038/gene.2014.43
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发表时间：
2014-07
影响因子：
5
通讯作者：
D.‐F. Zhang;D. Wang;Y. Li;Y-G Yao
中科院分区：
文献类型：
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作者：
D.‐F. Zhang;D. Wang;Y. Li;Y-G Yao
补体因子H （CFH）是补体系统稳态的重要调节因子，在麻风病中发挥多种作用。我们之前报道了CFH与麻风病的初步关联，但潜在的因果变异仍有待确定。在这项研究中，我们对1110名个体（527名麻风病患者和583名对照组）进行了精细映射关联分析，然后进行了生物信息学分析。我们发现典型的错义CFH变异与麻风没有关联，并且在麻风分枝杆菌中未检测到因子h结合蛋白。然而，观察到几个CFH内含子标签单核苷酸多态性与麻风病有很强的相关性（P Bonferroni< 0.003）。表达数量性状位点分析显示，这些麻风保护性等位基因与较高的CFH水平和较低的CFHR3（补体因子h相关3）水平相关。我们的研究结果表明，CFH变异可能通过改变CFH表达，导致补体活性的调节，而不是通过细菌结合介导免疫逃避，从而促进麻风病的发病。
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 (P Bonferroni< 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.