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- Peacock, Rachel E., et al.
(författare)
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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
- 1992
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 97:2-3, s. 171-185
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Peacock, Rachel E, et al.
(författare)
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Associations of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses
- 1994
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 46:4, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- Association studies were carried out in a sample of 86 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 at the apolipoprotein (apo) AI-CIII-AIV gene cluster on among-individual differences in plasma lipid and lipoprotein traits, the five high density lipoprotein (HDL) subclasses (2b to 3c), lipoprotein lipase (LPL) activity and presence and progression of atherosclerosis. Individuals were genotyped for four polymorphisms; 5'apoAI (G/A-75), 3'apoAI (PstI; P +/-), apoCIII (C/T1100) and apoCIII (PvuII; V +/-), using PCR-based techniques. Allele frequencies were similar in healthy individuals and patients (frequencies of alleles in combined population: 5'apoAI-A-75 = 0.14, 3'apoAI-P- = 0.05, apoCIII-T1100 = 0.27 and apoCIII-V- = 0.18). In the healthy individuals, levels of low density lipoprotein (LDL) triglycerides were significantly associated with genotypes of the apoCIII-PvuII polymorphism (p = 0.02), but no other associations were found between lipids or HDL subclasses and single polymorphisms in the apoAI-CIII-AIV gene cluster. Levels of triglycerides and very low density lipoprotein (VLDL) triglycerides were significantly higher in the presence of the haplotype defined by the presence of apoCIII-T1100 and common alleles of the other three polymorphisms, explaining 5.8% and 7.8% (p = 0.03 and 0.01), respectively, of sample variance. In the patients, no associations were found between lipids or HDL subclasses and variation at the apoAI-CIII-AIV gene cluster. Associations were also examined between levels of HDL subclasses and variation at the apoE (common isoforms), apoB (signal peptide and XbaI polymorphisms) and lipoprotein lipase (PvuII, HindIII and Serine447/Stop polymorphisms) gene loci. In the patient group only, levels of protein in HDL2b, HDL2a and HDL3b subclasses were significantly associated with genotypes of the LPL-HindIII polymorphism (22.1, 19.3 and 11.4%, respectively, of sample variance; p < 0.05). Finally, associations were examined between genotypes at the apoAI-CIII-AIV gene cluster and the extent of coronary atherosclerosis. Global severity of atherosclerosis at the first angiography was weakly associated with genotypes of the apoCIII-C/T1100 polymorphism, presence of the T1100 allele being associated with 53% lower median score (1.6 vs 0.75; p = 0.09).(ABSTRACT TRUNCATED AT 400 WORDS)
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