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 enzymedefined 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.
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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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