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.