An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum

Xin Long, Qian Chen, Jianping Zhao, Nicholas Rafaels, Priyanka Mathias, Huifang Liang, Joseph Potee, Monica Campbell, Bixiang Zhang, Li Gao, Steve N. Georas, Donata Vercelli, Terri L Beaty, Ingo Ruczinski, Rasika Mathias, Kathleen C. Barnes, Xiaoping Chen

Research output: Contribution to journalArticle

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 latestage 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.

Original languageEnglish (US)
Article numbere0135360
JournalPLoS One
Volume10
Issue number8
DOIs
StatePublished - Aug 10 2015

Fingerprint

Schistosoma japonicum
schistosomiasis
liver cirrhosis
Interleukin-13
Schistosomiasis
Polymorphism
Liver Cirrhosis
Liver
promoter regions
genetic polymorphism
Tissue
Plasmids
Luciferases
plasmids
luciferase
Nucleotides
Haplotypes
liver
single nucleotide polymorphism
Single Nucleotide Polymorphism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Long, X., Chen, Q., Zhao, J., Rafaels, N., Mathias, P., Liang, H., ... Chen, X. (2015). An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum. PLoS One, 10(8), [e0135360]. https://doi.org/10.1371/journal.pone.0135360

An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum. / Long, Xin; Chen, Qian; Zhao, Jianping; Rafaels, Nicholas; Mathias, Priyanka; Liang, Huifang; Potee, Joseph; Campbell, Monica; Zhang, Bixiang; Gao, Li; Georas, Steve N.; Vercelli, Donata; Beaty, Terri L; Ruczinski, Ingo; Mathias, Rasika; Barnes, Kathleen C.; Chen, Xiaoping.

In: PLoS One, Vol. 10, No. 8, e0135360, 10.08.2015.

Research output: Contribution to journalArticle

Long, X, Chen, Q, Zhao, J, Rafaels, N, Mathias, P, Liang, H, Potee, J, Campbell, M, Zhang, B, Gao, L, Georas, SN, Vercelli, D, Beaty, TL, Ruczinski, I, Mathias, R, Barnes, KC & Chen, X 2015, 'An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum', PLoS One, vol. 10, no. 8, e0135360. https://doi.org/10.1371/journal.pone.0135360
Long, Xin ; Chen, Qian ; Zhao, Jianping ; Rafaels, Nicholas ; Mathias, Priyanka ; Liang, Huifang ; Potee, Joseph ; Campbell, Monica ; Zhang, Bixiang ; Gao, Li ; Georas, Steve N. ; Vercelli, Donata ; Beaty, Terri L ; Ruczinski, Ingo ; Mathias, Rasika ; Barnes, Kathleen C. ; Chen, Xiaoping. / An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum. In: PLoS One. 2015 ; Vol. 10, No. 8.
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title = "An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum",
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 latestage 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.",
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AU - Long, Xin

AU - Chen, Qian

AU - Zhao, Jianping

AU - Rafaels, Nicholas

AU - Mathias, Priyanka

AU - Liang, Huifang

AU - Potee, Joseph

AU - Campbell, Monica

AU - Zhang, Bixiang

AU - Gao, Li

AU - Georas, Steve N.

AU - Vercelli, Donata

AU - Beaty, Terri L

AU - Ruczinski, Ingo

AU - Mathias, Rasika

AU - Barnes, Kathleen C.

AU - Chen, Xiaoping

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N2 - 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 latestage 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.

AB - 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 latestage 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.

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