Lipoprotein Lipase Gene Polymorphisms Research Articles

Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population.

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and XbaI polymorphism, the apo E polymorphism and two polymorphism of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and HindIII/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p < 0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and PvuII/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The epsilon 4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p < 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden.

Association studies were carried out on a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms (PvuII, HindIII and Serine447-Stop) at the lipoprotein lipase (LPL) gene locus on among-individual differences in plasma lipid traits and progression of atherosclerosis. Significant linkage disequilibrium was detected between any two of these polymorphisms, with the Stop447 allele being only found on the same chromosome as the rare alleles (no cutting sites) of the PvuII and HindIII polymorphisms. In the healthy individuals, weak associations were found between genotypes of the HindIII polymorphism and triglycerides and the PvuII polymorphism and high density lipoprotein cholesterol explaining 7.4% and 5.6% of sample variance (P = 0.03 and 0.09), respectively. No associations were found between these traits and genotypes of the Serine447-Stop substitution, and thus it is unlikely to be the cause of the associations seen with the PvuII and HindIII polymorphisms even though it truncates the enzyme amino acid sequence. The presence of the rare allele, H-, of the HindIII polymorphism was associated with a smaller variance in triglycerides and both cholesterol and triglycerides in the very low density lipoprotein fraction, and with larger interdependent variation between these lipid traits, and also between LPL activity and these lipid traits. This implies that the H- allele, rather than the Stop447 allele, has the major impact on interdependence between traits which are directly or indirectly influenced by LPL activity. In the healthy individuals who were carriers of the apolipoprotein E2 allele, the inter-dependence between LPL activity and lipid traits was significantly smaller, and that between high density lipoprotein cholesterol and both cholesterol and triglycerides in the very low density lipoprotein fraction was much larger compared with non-carriers (P < 0.05). No significant associations were found between lipid traits or lipase activity and genotypes of the Serine447-Stop substitution. However, in the patients, global severity of coronary atherosclerosis at the first angiography was significantly associated with haplotype combinations of the HindIII and the Serine447-Stop polymorphisms, with the H-Stop haplotype being associated with the highest median score (P = 0.02). The data suggest that variation at the LPL gene locus is associated with a pleiotropic effect, that is not directly mediated by changes in lipids, on severity of coronary atherosclerosis.

DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels

Lipoprotein lipase (LPL) plays a central role in the metabolism of lipoproteins by hydrolyzing the core triglycerides of circulating very low density lipoproteins and chylomicrons. The enzyme is encoded by a gene about 30 kb in size located on the short arm of human chromosome 8. We have determined the locations of the four common DNA polymorphisms along the gene, including a polymorphism that occurred only among an American black population examined. These restriction site polymorphisms were used for haplotype analysis of Mediterranean and US black families. Estimation of the extent of nonrandom association between these polymorphisms indicated considerable linkage disequilibrium between these sites. No correlation was observed between the level of linkage disequilibrium and the physical distance of the polymorphic sites. The polymorphism information content of the haplotypes ranged from 0.65 to 0.74, thereby constituting a relatively useful genetic marker on chromosome 8. We tested for possible associations between the polymorphisms and circulating lipoprotein phenotypes in a population of 139 Caucasians undergoing coronary arteriography and 50 of their spouses. Some possibly significant associations between LPL gene polymorphisms and levels of high density lipoprotein cholesterol (P = 0.015) and total plasma cholesterol (P = 0.025) were observed. In contrast to a previous report, we found no significant associations with the levels of plasma triglycerides.