Lipoprotein lipase HindIII polymorphism influences HDL-cholesterol levels in statin-treated patients with coronary artery disease.
BACKGROUND
HDL-cholesterol (HDL-C) is a recognized athero-protective factor and low levels of HDL-C occur frequently in patients with coronary artery disease. Regulation of HDL-C level most probably results from the interaction of genes involved in lipoprotein metabolism and also from non-genetic factors. We studied associations and interactions among HindIII polymorphisms of the lipoprotein lipase gene LPL and selected non-genetic factors with respect to HDL-C levels in patients with coronary artery disease.


METHODS
288 Slovak patients (35% women) with documented coronary artery disease, age (mean +/- SEM) 60 +/- 1 years and BMI 29 +/- 0.3 kg/m(2), were examined and genotyped for LPL HindIII (rs320) using a PCR/RFLP method. HDL-C levels were determined in a direct enzymatic assay.


RESULTS
In the sample overall there were no significant differences across the LPL genotypes in adjusted HDL-C levels or in other lipids, although a trend toward higher HDL-C and lower triglycerides in H-H- homozygotes was observed. Multiple linear regression identified a significant interaction between LPL HindIII and statin treatment, which together with sex and diabetes explained 12.1% of HDL-C variance. Accordingly, in statin-treated patients we observed significant stepwise increments of the HDL-C level related to the increasing number of H- alleles (P = 0.04 for linear trend), whereas no such association was observed in patients without hypolipidemic treatment. H-H- homozygotes had a 16% (0.19 mmol/l) higher level of HDL-C than the H+H+ homozygotes (P = 0.06).


CONCLUSIONS
HDL-C may be influenced by an interaction between statin treatment and LPL HindIII genotype. However, the effect of this interaction appears to be small when compared with the effect of non-genetic factors. This finding requires replication in a pharmacogenetic study.
Javorský
Martin
M
Department of Internal Medicine 4, Safárik University School of Medicine, Kosice, Slovak Republic.
Gasperíková
Daniela
D
Ukropec
Jozef
J
Sedláková
Barbora
B
Riecanský
Igor
I
Krizanová
Ol'ga
O
Seböková
Elena
E
Dobríková
Martina
M
Klimes
Iwar
I
Tkác
Ivan
I
D000368:Aged; D000483:Alleles; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D003430:Cross-Sectional Studies; D015247:Deoxyribonuclease HindIII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D018154:Slovakia
D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008071:Lipoprotein Lipase; D015247:Deoxyribonuclease HindIII