Abstract
The aim of this study was to determine whether two polymorphisms in the gene encoding IL13 previously associated with Schistosoma hematobium (S. hematobium) and S. mansoni infection are associated with S. japonicum infection. Single nucleotide polymorphisms (SNPs) rs1800925 (IL13/-1112C>T) and rs20541 (IL13R130Q) were genotyped in 947 unrelated individuals (307 chronically infected, 339 late-stage with liver fibrosis, 301 uninfected controls) from a schistosomiasis-endemic area of Hubei province in China. Regression models were used to evaluate allelic and haplotypic associations with chronic and late-stage schistosomiasis adjusted for non-genetic covariates. Expression of IL-13 was measured in S. japonicun-infected liver fibrosis tissue and normal liver tissue from uninfected controls by immunohistochemistry (IHC). The role of rs1800925 in IL-13 transcription was further determined by Luciferase report assay using the recombinant PGL4.17-rs180092 plasmid. We found SNP rs1800925T was associated with late-stage schistosomiasis caused by S. japonicum but not chronic schistosomiasis (OR = 1.39, 95%CI = 1.02–1.91, p = 0.03) and uninfected controls (OR = 1.49, 95%CI = 1.03–2.13, p = 0.03). Moreover, the haplotype rs1800925T-rs20541C increased the risk of disease progression to late-stage schistosomiasis (OR = 1.46, p = 0.035), whereas haplotype rs1800925C-rs20541A showed a protective role against development of late-stage schistosomiasis (F = 0.188, OR = 0.61, p = 0.002). Furthermore, S. japonicum-induced fibrotic liver tissue had higher IL13 expression than normal liver tissue. Plasmid PGL4.17-rs1800925T showed a stronger relative luciferase activity than Plasmid PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. In conclusion, the functional IL13 polymorphism, rs1800925T, previously associated with risk of schistosomiasis, also contributes to risk of late-stage schistosomiasis caused by S. japonicum.
Highlights
Schistosomiasis, a neglected parasitic disease, is highly endemic in areas along the Yangtze River in China, where nearly half a million people are infected with S. japonicum and 65 million are at risk of infection [1,2,3,4]
We further explored the potential function of Single nucleotide polymorphisms (SNPs) rs1800925 in hepatic cell lines and embryonic kidney cell lines and measured IL-13 expression in fibrotic liver tissues from S. japonicum-infected patients and normal liver tissues from uninfected controls
We demonstrate a functional polymorphism in IL13, rs1800925 (IL13/1112C>T), previously associated with risk of schistosomiasis, increased the risk of development of late-stage schistosomiasis
Summary
Schistosomiasis, a neglected parasitic disease, is highly endemic in areas along the Yangtze River in China, where nearly half a million people are infected with S. japonicum and 65 million are at risk of infection [1,2,3,4]. Over the past 50 years, great progress has been made in China in reducing disease transmission using conventional chemotherapy (Praziquantel), eradication of the intermediate snail host, and management of domestic animals including dogs, water buffalo and yellow cattle [1, 4, 5] While these measures have reduced the number of new cases of schistosomiasis, complications associated with chronic S. japonicum infection have increased [6]. 5%-13% of S. japonicum infections may develop in end-stage liver diseases [7, 8], including cirrhosis, portal hypertension, splenomegaly, and ascites, and eventually lead to death It remains unknown why certain patients develop severe liver complications and others do not, despite living in a similar endemic environment
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