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CLINICAL STUDIES

Association of lipoprotein lipase gene polymorphisms with coronary artery disease

Jeffrey L. Anderson, MD, FACC^* , Gretchen J. King, PhD^* , Tami L. Bair, BS^* , Sidney P. Elmer, BS^* , Joseph B. Muhlestein, MD, FACC^* , Jessica Habashi, BS^* , Lori Mixson, PhD and John F. Carlquist, PhD^*

^* Department of Medicine (Cardiology), University of Utah, LDS Hospital, Salt Lake City, Utah, USA
Department of Pathology, University of Utah, LDS Hospital, Salt Lake City, Utah, USA
Merck Research Laboratories, West Point, Pennsylvania, USA

Manuscript received July 14, 1998; revised manuscript received October 19, 1998, accepted December 11, 1998.

Reprint requests and correspondence: Dr. Jeffrey L. Anderson, University of Utah, Division of Cardiology, 50 N. Medical Drive, Salt Lake City, Utah 84132

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 and Acronyms   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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