title: Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.
abstract: BACKGROUND
  Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.
  
  
  RESULTS
  Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups.
  
  
  CONCLUSIONS
  We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco (UFPE), Recife, Brazil.
authors: Caíque Silveira
authors: CS
authors: Martins da Fonseca
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco (UFPE), Recife, Brazil.
authors: Adenor Almeida
authors: AA
authors: Pimenta Filho
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco (UFPE), Recife, Brazil.
authors: Bianka Santana
authors: BS
authors: dos Santos
authors: Colegiado de Medicina, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina, Brazil.
authors: César Augusto
authors: CA
authors: da Silva
authors: Departamento de Medicina Clínica, Centro de Ciências da Saúde, Hospital das Clinicas, UFPE, Recife, Brazil.
authors: Ana Lúcia Coutinho
authors: AL
authors: Domingues
authors: Division of Medicine, University College London Medical School, Royal Free Campus, London, United Kingdom.
authors: James Stuart
authors: JS
authors: Owen
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco (UFPE), Recife, Brazil.
authors: Vera Lúcia de Menezes
authors: VL
authors: Lima
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics* / Q000469:parasitology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012555:Schistosomiasis mansoni / Q000097:blood* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides