Clinical Studies
Association of lipoprotein lipase gene polymorphisms with coronary artery disease

https://doi.org/10.1016/S0735-1097(98)00677-9Get rights and content
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Abstract

OBJECTIVES

The purpose of this study was to test whether the HindIII (+) and PvuII (−) or (+) restriction enzyme–defined alleles are associated with angiographic coronary artery disease (CAD).

BACKGROUND

Lipoprotein lipase (LPL) plays a central role in lipid metabolism, hydrolyzing triglyceride in chylomicrons and very low density lipoproteins. Polymorphic variants of the LPL gene are common and might affect risk of CAD.

METHODS

Blood was drawn from 725 patients undergoing coronary angiography. Leukocyte deoxyribonucleic acid segments containing the genomic sites were amplified by the polymerase chain reaction and digested, and polymorphisms were identified after electrophoresis in 1.5% agarose gel.

RESULTS

In no-CAD control subjects (n = 168), HindIII (−) and (+) allelic frequencies were 28.6% and 71.4%, and (−) and (+) alleles were carried by 44.0% and 86.9% of subjects, respectively. Control PvuII (−) and (+) allelic frequencies were 41.7% and 58.3%, and (−) and (+) alleles were carried by 64.3% and 81.0%, respectively. In CAD patients (>60% stenosis; n = 483), HindIII (+) allelic carriage was increased (93.8% of patients, odds ratio [OR] = 2.28, confidence interval [CI] 1.27 to 4.00). Also, PvuII (−) allelic carriage tended to be more frequent in CAD patients (OR = 1.33, CI 0.92 to 1.93). Adjusted for six CAD risk factors and the other polymorphism, HindIII (+) carriage was associated with an OR = 2.86, CI 1.50 to 5.42, p = 0.0014, and PvuII (−) carriage, OR = 1.42, CI 0.95 to 2.12, p = 0.09. The two polymorphisms were in strong linkage disequilibrium, and a haplotype association was suggested.

CONCLUSIONS

The common LPL polymorphic allele, HindIII (+), is moderately associated with CAD, and the PvuII (−) allele is modestly associated (trend). Genetic variants of LPL deserve further evaluation as risk factors for CAD.

Abbreviations

CAD
coronary artery disease
CI
confidence intervals
DNA
deoxyribonucleic acid
HDL
high density lipoprotein
LDL
low density lipoprotein
LPL
lipoprotein lipase
MI
myocardial infarction
OR
odds ratio
VLDL
very low density lipoprotein

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This study was funded in part by a grant from Deseret Foundation, Salt Lake City, Utah.