Abstract
BackgroundSchistosomiasis 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.Methodology/Principal FindingsBlood 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.Conclusion/SignificanceWe 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.
Highlights
Schistosomiasis, caused by Schistosoma mansoni worms, is one of the most prevalent parasitic diseases
Our report is the first to identify a host genetic factor, Apolipoprotein E (APOE) polymorphism, which influences the extent and nature of plasma lipid changes associated with schistosomiasis mansoni
Several studies have shown the APOE genotype to influence infection susceptibility and damage in certain diseases caused by viruses, including human immunodeficiency virus [18] and hepatitis C [26,35] and B [36], protozoa [23] and fungi [24]
Summary
Schistosomiasis, caused by Schistosoma mansoni worms, is one of the most prevalent parasitic diseases. Previous studies have reported that human schistosomiasis alters plasma lipid composition [6,7,8,9] and metabolism [10]. It is generally agreed that S. mansoni infection reduces levels of plasma cholesterol and triglycerides in both rodents [11,12] and non-human primates [13,14]. Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. 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
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