title: A potential screening factor for accumulation of cholesteyl ester transfer protein deficiency in East Asia: Schistosoma japonicum.
abstract: Cholesteryl ester transfer protein (CETP)-deficiency manifests a unique plasma lipoprotein profile without other apparent symptoms. It is highly common in East Asia while rather rare anywhere else. A potential environmental screening factor(s) may therefore contribute to this eccentric distribution, such as its selective advantage against a regional illness, most likely an infectious disease, in relation to plasma lipoproteins. Blood flukes use the host plasma lipoproteins as nutrient sources through the lipoprotein receptor-like systems. Its Asian-specific species, Schistosoma (S) japonicum, which has been endemic in East Asia, takes up cholesteryl ester (CE) from high-density lipoprotein (HDL) for the embryonation of their eggs to miracidia, a critical step of the hepatic pathogenesis of this parasite, but poorly from HDL of CETP-deficiency. CD36-related protein (CD36RP) was cloned from the adults and the eggs of S. japonicum, with 1880-bp encoding 506 amino-acid residues exhibiting the CD36 domains and two transmembrane regions. Its extracellular domain selectively bound human HDL but neither LDL nor CETP-deficiency HDL, and the antibody against the extracellular domain suppressed the selective HDL-CE uptake and embryonation of the eggs. When infected with S. japonicum, wild-type mice developed less hepatic granulomatosis than CETP-transgenic mice by the ectopic egg embryonation. CD36RP is thus a candidate receptor of S. japonicum to facilitate uptake of HDL-CE necessary for egg embryonation. Abnormal HDL caused by CETP-deficiency retards this process and thereby protects the patients from development of hepatic lesions. S. japonicum infection is a potential screening factor for high prevalence of CETP deficiency in East Asia.
authors.affiliation: Nutritional Health Science Research Center, Chubu University, Matsumoto-cho 1200, Kasugai 487-8501, Japan. Electronic address: syokoyam@isc.chubu.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001208:Asia; D018955:CD36 Antigens / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008822:Mice, Transgenic; D010063:Ovum / Q000254:growth & development / Q000378:metabolism; D012549:Schistosoma japonicum / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D012554:Schistosomiasis japonica / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology
chemical_list: D018955:CD36 Antigens; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL
keywords: CETP; CETP deficiency; Egg embryonation; HDL; Liver; Schistosoma