TY - JOUR
T1 - Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease
T2 - The Veterans Affairs HDL Intervention Trial
AU - Brousseau, Margaret E.
AU - Goldkamp, Allison L.
AU - Collins, Dorothea
AU - Demissie, Serkalem
AU - Connolly, Allison C.
AU - Cupples, L. Adrienne
AU - Ordovas, Jose M.
AU - Bloomfield, Hanna E.
AU - Robins, Sander J.
AU - Schaefer, Ernst J.
PY - 2004/10
Y1 - 2004/10
N2 - 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; ≤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.
AB - 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; ≤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.
KW - Fibrate
KW - Genetics
KW - High density lipoprotein cholesterol
KW - Lipids
UR - http://www.scopus.com/inward/record.url?scp=16644379916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=16644379916&partnerID=8YFLogxK
U2 - 10.1194/jlr.M400152-JLR200
DO - 10.1194/jlr.M400152-JLR200
M3 - Article
C2 - 15292370
AN - SCOPUS:16644379916
SN - 0022-2275
VL - 45
SP - 1885
EP - 1891
JO - Journal of lipid research
JF - Journal of lipid research
IS - 10
ER -