Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women.
OBJECTIVE
A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor alpha gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. Subjects Postmenopausal Caucasian women (n = 208) participating in a placebo-controlled randomized trial of 3.2 years of hormone therapy (HT).


METHODS
Plasma triglyceride (TG), remnant lipoprotein cholesterol (RLP-C), and high-density lipoprotein cholesterol (HDL-C) levels and HDL subpopulations were assessed at baseline and at follow up. Single nucleotide polymorphisms (SNPs) in ESR1 and in the ATP binding cassette A1 (ABCA1), cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), and scavenger receptor class B type I (SRB1) genes were assessed for their association with baseline plasma levels and HT-related changes in levels of RLP-C and HDL subpopulations.


RESULTS
Carriers of the ESR1 PvuII or IVS1-1505 variants had lower plasma TG concentrations and higher plasma HDL-C and alpha-1 and prealpha-1 HDL particle levels at baseline and showed greater increases in HDL-C, apo A-I and alpha-1 particle levels after HT than wild-type carriers. Carriers of the N291S and D9N variants in the LPL gene had significantly higher remnant lipoproteins and lower alpha-2 HDL particle levels at baseline. The CETP TaqIB SNP was a significant determinant of baseline plasma HDL-C and HDL subpopulation profile.


CONCLUSIONS
Single nucleotide polymorphisms in ESR1, CETP and LPL had significant effects on baseline plasma levels of TG-rich and HDL subpopulations. With the exception of ESR1 SNPs, variation in genes involved in lipid metabolism has a very modest effect on lipoprotein response to HT.
Lamon-Fava
Stefania
S
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Asztalos
Bela F
BF
Howard
Timothy D
TD
Reboussin
David M
DM
Horvath
Katalin V
KV
Schaefer
Ernst J
EJ
Herrington
David M
DM
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D047628:Estrogen Receptor alpha / Q000235:genetics; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008049:Lipase / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause / Q000097:blood*; D051122:Scavenger Receptors, Class B / Q000235:genetics; D014280:Triglycerides / Q000097:blood
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004966:Estrogens, Conjugated (USP); C504173:LIPC protein, human; D008074:Lipoproteins; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D017258:Medroxyprogesterone Acetate; D008049:Lipase; D008071:Lipoprotein Lipase