Association of lipoprotein lipase gene polymorphisms with coronary artery disease.
OBJECTIVE
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 PvulI (-) 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.
Anderson
J L
JL
Department of Medicine (Cardiology), University of Utah, LDS Hospital, Salt Lake City 84132, USA.
King
G J
GJ
Bair
T L
TL
Elmer
S P
SP
Muhlestein
J B
JB
Habashi
J
J
Mixson
L
L
Carlquist
J F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012680:Sensitivity and Specificity
D008071:Lipoprotein Lipase