Human Genet：姚永刚等发现补体通路基因遗传变异可影响麻风易感

麻风由麻风分枝杆菌感染引起，是一种古老的慢性传染病。患者通常会出现肢端残疾、畸形、失明甚至毁容等症状，饱受社会的歧视。流行病学调查显示约5%的人群对麻风分枝杆菌易感。麻风临床症状复杂，其发生发展与机体的遗传背景以及免疫状态有关。云南省是我国麻风重灾区，目前仍有若干地区尚未达到基本消灭麻风的目标。

补体系统是连接机体先天免疫与后天免疫的桥梁，表现出丰富的免疫多样性与遗传多态性，影响机体对于传染病的易感。前人关于补体系统与麻风易感的研究多基于小样本，得到的结论在不同研究中存在差异。姚永刚课题组的博士生张登峰和合作者针对来自云南玉溪地区较大样本的麻风病例与正常对照人群，开展了补体系统相关基因遗传变异与麻风易感的关联分析，发现补体lectin通路基因FCN2和MBL2、补体旁路途径关键调控基因CFH的遗传变异影响麻风易感，且FCN2和MBL2基因低转录活性的启动子单倍型是少菌型麻风的风险因素。

该结果提示补体系统在麻风易感中发挥重要作用。研究结果近期发表在国际期刊Human Genetics (全文链接：http：//link.springer.com/article/10.1007%2Fs00439-013-1273-8)

该研究得到国家自然科学基金委、云南省和中科院的资助。

doi:10.1007%2Fs00439-013-1273-8
PMC:
PMID:

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

Deng-Feng Zhang, Xian-Qiong Huang, Dong Wang, Yu-Ye Li, Yong-Gang Yao

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.