title: The role of ST2 and ST2 genetic variants in schistosomiasis.
abstract: BACKGROUND
  Chronic schistosomiasis and its severe complication, periportal fibrosis, are characterized by a predominant Th2 response. To date, specific single nucleotide polymorphisms in ST2 have been some of the most consistently associated genetic variants for asthma.
  
  
  OBJECTIVE
  We investigated the role of ST2 (a receptor for the Th2 cytokine IL-33) in chronic and late-stage schistosomiasis caused by Schistosoma japonicum and the potential effect of ST2 genetic variants on stage of disease and ST2 expression.
  
  
  METHODS
  We recruited 947 adult participants (339 with end-stage schistosomiasis and liver cirrhosis, 307 with chronic infections without liver fibrosis, and 301 health controls) from a S japonicum-endemic area (Hubei, China). Six ST2 single nucleotide polymorphisms were genotyped. Serum soluble ST2 (sST2) was measured by ELISA, and ST2 expression in normal liver tissues, Hepatitis B virus-induced fibrotic liver tissues, and S japonicum-induced fibrotic liver tissues was measured by immunohistochemistry.
  
  
  RESULTS
  We found sST2 levels were significantly higher in the end-stage group (36.04 [95% CI, 33.85-38.37]) compared with chronic cases and controls (22.7 [95% CI, 22.0-23.4], P < 1E-10). In addition, S japonicum-induced fibrotic liver tissues showed increased ST2 staining compared with normal liver tissues (P = .0001). Markers rs12712135, rs1420101, and rs6543119 were strongly associated with sST2 levels (P = 2E-10, 5E-05, and 6E-05, respectively), and these results were replicated in an independent cohort from Brazil living in a S mansoni endemic region.
  
  
  CONCLUSIONS
  We demonstrate for the first time that end-stage schistosomiasis is associated with elevated sST2 levels and show that ST2 genetic variants are associated with sST2 levels in patients with schistosomiasis.
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinical Study Center of Liver Surgery in Hubei Province, Wuhan, China; Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Xin
authors.initials: X
authors.lastname: Long
authors.affiliation: Biomedical Informatics and Personalized Medicine, University of Colorado School of Medicine, Aurora, Colo.
authors.forename: Michelle
authors.initials: M
authors.lastname: Daya
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinical Study Center of Liver Surgery in Hubei Province, Wuhan, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rafaels
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinical Study Center of Liver Surgery in Hubei Province, Wuhan, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Liang
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Joseph
authors.initials: J
authors.lastname: Potee
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
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, China; Clinical Study Center of Liver Surgery in Hubei Province, Wuhan, China.
authors.forename: Bixiang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Servico de Imunologia, Hospital Universitario Professor Edgard Santos, Salvador, Brazil.
authors.forename: Maria Ilma
authors.initials: MI
authors.lastname: Araujo
authors.affiliation: Instituto Goncalo Moniz, Fundacao Oswaldo Cruz - Bahia, Salvador, Brazil.
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Oliveira
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Md.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.affiliation: Department of Medicine, University of Rochester Medical Center, Rochester, NY.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, Ariz.
authors.forename: Donata
authors.initials: D
authors.lastname: Vercelli
authors.affiliation: Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Md.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: Kathleen.Barnes@UCDenver.edu.
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, China; Clinical Study Center of Liver Surgery in Hubei Province, Wuhan, China. Electronic address: chenxp@medmail.com.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: chenqian201579@yahoo.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D001938:Brazil / Q000453:epidemiology; D002681:China / Q000453:epidemiology; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D019353:Endemic Diseases; D005260:Female; D005355:Fibrosis; D005838:Genotype; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood / Q000235:genetics*; D000067596:Interleukin-33 / Q000378:metabolism; D008099:Liver / Q000469:parasitology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012549:Schistosoma japonicum / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology*; D012552:Schistosomiasis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33
keywords: ST2; Schistosoma japonicum; liver cirrhosis immunohistochemistry; sST2