Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease: the Veterans Affairs HDL Intervention Trial.
Our goal was to further define the role of LPL gene polymorphisms in coronary heart disease (CHD) risk. We determined the frequencies of three LPL polymorphisms (D9N, N291S, and S447X) in 899 men from the Veterans Affairs HDL Intervention Trial (VA-HIT), a study that examined the potential benefits of increasing HDL with gemfibrozil in men with established CHD and low high density lipoprotein cholesterol (HDL-C; < or =40 mg/dl), and compared them with those of men without CHD from the Framingham Offspring Study (FOS). In VA-HIT, genotype frequencies for LPL D9N, N291S, and S447X were 5.3, 4.5, and 13.0%, respectively. These values differed from those for men in FOS having an HDL-C of >40, who had corresponding values of 3.2% (P = 0.06), 1.5% (P < 0.01), and 18.2% (P < 0.01). On gemfibrozil, carriers of the LPL N9 allele in VA-HIT had lower levels of large LDL (-32%; P < 0.01) but higher levels of small, dense LDL (+59%; P < 0.003) than did noncarriers. Consequently, mean LDL particle diameter was smaller in LPL N9 carriers than in noncarriers (20.14 +/- 0.87 vs. 20.63 +/- 0.80 nm; P < 0.003). In men with low HDL-C and CHD: 1) the LPL N9 and S291 alleles are more frequent than in CHD-free men with normal HDL-C, whereas the X447 allele is less frequent, and 2) the LPL N9 allele is associated with the LDL subclass response to gemfibrozil.
Lipid Metabolism Laboratory, Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, and Department of Medicine, New England Medical Center, Boston, MA, USA. margaret.brousseau@tufts.edu
Margaret E
ME
Brousseau
Allison L
AL
Goldkamp
Dorothea
D
Collins
Serkalem
S
Demissie
Allison C
AC
Connolly
L Adrienne
LA
Cupples
Jose M
JM
Ordovas
Hanna E
HE
Bloomfield
Sander J
SJ
Robins
Ernst J
EJ
Schaefer
D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D003327:Coronary Disease / Q000201:enzymology / Q000235:genetics*; D015248:Gemfibrozil / Q000494:pharmacology; D005787:Gene Frequency; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010316:Particle Size; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D008071:Lipoprotein Lipase; D015248:Gemfibrozil