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

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.

Mannose-binding Lectin (MBL) as a susceptible host factor influencing Indian Visceral Leishmaniasis

“…In HapMap database, the investigated variant -78C/T was widely distributed across all ethnicities and was observed to be in high LD with another variant +4P/Q in the 5' UTR region of exon 1 especially in Han Chinese population. However, no significant associations with leprosy was reported in Han Chinese population [39]. Also in this study, the investigated variants +4P/Q and -78C/T were in strong LD.…”

“…The contribution of this studied MBL2 -78C/T with other diseases is limited. This particular MBL2 -78C/T variant has been reported in Han Chinese and Gabonese populations [39,40]. In HapMap database, the investigated variant -78C/T was widely distributed across all ethnicities and was observed to be in high LD with another variant +4P/Q in the 5' UTR region of exon 1 especially in Han Chinese population.…”

Association between mannose-binding lectin variants, haplotypes and risk of hepatocellular carcinoma: A case-control study

“…The promoter 1 regulates most part of MBL2 transcription, therefore, the polymorphisms in promoter 1 would significantly affect the serum level of MBL2, and among 2 variants identified, it is suggested that −221 Y/X play a more important role. For example, −221 Y/X has been linked with chronic infection in some clinical studies, in addition, a genome wide association study reported the association between −221 Y/X polymorphism and the susceptibility of leprosy among Chinese population9. Our analysis observed the positive correlation between both −550 and −221 polymorphisms and the risk of HCC, the adjusted ORs were 1.61 (95%CI = 1.00–2.57) and 5.67 (95%CI = 1.82–17.67), respectively.…”

The Lack of Association between <b><i>FCN2</i></b> Gene Promoter Region Polymorphisms and Dental Caries in Polish Children

“…Several studies investigated the association of FCN2 functional polymorphisms and/or ficolin-2 serum levels with different infectious diseases, including respiratory infections [Atkinson et al, 2004;Ruskamp et al, 2009], pneumonia [Chalmers et al, 2014], invasive pneumococcal disease [Chapman et al, 2007], pulmonary tuberculosis [Luo et al, 2013;Xu et al, 2015], leprosy [de MessiasReason et al, 2009;Zhang et al, 2013], hepatitis B [Hoang et al, 2011;Chen et al, 2015], leishmaniasis [Assaf et al, 2012;Mishra et al, 2015], schistosomiasis [Ouf et al, 2012] or autoimmune diseases with bacterial involvement, such as rheumatic fever and chronic rheumatic heart disease .…”