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 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.
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China; Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Long
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rafaels
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Mathias
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Liang
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Potee
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Bixiang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Donata
authors.initials: D
authors.lastname: Vercelli
authors.affiliation: Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Rasika
authors.initials: R
authors.lastname: Mathias
authors.affiliation: Johns Hopkins Asthma & Allergy Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006239:Haplotypes; D006790:Host-Parasite Interactions; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D012549:Schistosoma japonicum / Q000472:pathogenicity* / Q000502:physiology; D012554:Schistosomiasis japonica / Q000150:complications / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: C578095:IL13 protein, human; D018793:Interleukin-13