TY - JOUR
T1 - Genetic variation of PLTP modulates lipoprotein profiles in hypoalphalipoproteinemia
AU - Aouizerat, Bradley E.
AU - Engler, Mary B.
AU - Natanzon, Yanina
AU - Kulkarni, Medha
AU - Song, James
AU - Eng, Celeste
AU - Huuskonen, Jarkko
AU - Rivera, Christopher
AU - Poon, Annie
AU - Bensley, Matt
AU - Sehnert, Amy
AU - Zellner, Christian
AU - Malloy, Mary
AU - Kane, John
AU - Pullinger, Clive R.
PY - 2006/4
Y1 - 2006/4
N2 - Phospholipid transfer protein (PLTP) participates in key processes in lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. The impact of PLTP on reverse cholesterol transport suggests that the gene may harbor sequence anomalies that contribute to disorders of HDL metabolism. The human PLTP gene was screened for sequence anomalies by DNA melting analysis in 276 subjects with hypoalphalipoproteinemia (HA) and 364 controls. The association with plasma lipid parameters was evaluated. We discovered 18 sequence variations, including four missense mutations and a novel polymorphism (c.-34G>C). In healthy controls, the c.-34G>C minor allele was associated with higher high density lipoprotein-cholesterol (HDL-C) and was depleted in subjects with HA. Linear regression models predict that possession of the rare allele decreases plasma triglyceride (TG) and TG/HDL-C and increases HDL-C independent of TG. Decreased PLTP activity was observed in one (p.R235W) of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations in an in vitro activity assay. These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism.
AB - Phospholipid transfer protein (PLTP) participates in key processes in lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. The impact of PLTP on reverse cholesterol transport suggests that the gene may harbor sequence anomalies that contribute to disorders of HDL metabolism. The human PLTP gene was screened for sequence anomalies by DNA melting analysis in 276 subjects with hypoalphalipoproteinemia (HA) and 364 controls. The association with plasma lipid parameters was evaluated. We discovered 18 sequence variations, including four missense mutations and a novel polymorphism (c.-34G>C). In healthy controls, the c.-34G>C minor allele was associated with higher high density lipoprotein-cholesterol (HDL-C) and was depleted in subjects with HA. Linear regression models predict that possession of the rare allele decreases plasma triglyceride (TG) and TG/HDL-C and increases HDL-C independent of TG. Decreased PLTP activity was observed in one (p.R235W) of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations in an in vitro activity assay. These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism.
KW - Atherosclerosis
KW - Cardiovascular diseases
KW - Dyslipidemia
KW - Genetic polymorphism
KW - Phospholipid transfer protein
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U2 - 10.1194/jlr.M500476-JLR200
DO - 10.1194/jlr.M500476-JLR200
M3 - Article
C2 - 16388083
AN - SCOPUS:33645527386
SN - 0022-2275
VL - 47
SP - 787
EP - 793
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 4
ER -