Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein transport genes have been used to make either transgenic or knockout mice with altered lipoprotein levels and metabolism. These models have provided information in at least three major issues. First, transgenic mice allow to study gene expression regulation. This approach has been helpful in identifying tissue specific expression of two clusters of apolipoprotein genes apo E/CI/CII and apo AI/CIII/AIV. Another example is the identification of a cis-acting region controlling transcription of the CETP gene in response to diet. Second, transgenic mice model provides relevant insights into lipoprotein metabolism: the structural role of human apo AII, the effect of apo AI on HDL subfractions distribution, the contribution of apo CIII to hypertriglyceridemia, and by contrast of apo E in the clearance of atherogenic TG rich lipoproteins, the role of CETP in the balance of LDL and HDL concentration and distribution. Finally, certain strains of mice under specific conditions of diet develop atherosclerotic lesions which have been shown to be reduced in human apo AI transgenic animals. However, the best mouse model for further investigation of human atherosclerosis seems to be apo E knockout mice.
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PMID:[Value of transgenic mouse as model for the study of human lipoprotein metabolism]. 757 8

Alagille syndrome is frequently associated with hyperlipidemia and xanthoma. The aim of the study was to assess the lipid profile (plasma lipoproteins, apolipoproteins (apo)) and lecithin cholesterol acyl transferase (LCAT) activity, with and without treatment with cholestyramine in Alagille syndrome. Five children (mean age = 6 +/- 4 years) with Alagille syndrome were studied at two different times while receiving no treatment, and while receiving cholestyramine. They were compared with 12 normal controls, who were not different from patients for age and sex. In Alagille syndrome, total serum cholesterol, triglycerides and phospholipids were elevated compared with the controls (P < 0.008). VLDL-cholesterol, LDL-cholesterol, HDL-triglycerides, LDL-triglycerides and VLDL-phospholipids were higher, whereas HDL-cholesterol was lower than controls (P < 0.03). Apo B, CIII, E and lipoprotein particles Lp AI were higher (P < 0.001), whereas Lp AI:AII was lower than controls (P < 0.03). Lipoprotein-X was present in the 5 children with Alagille syndrome and explained in part the elevation of plasma cholesterol, phospholipids, and apo CIII. LCAT activity was decreased (P < 0.01) and might cause some abnormalities of HDL with lower cholesterol, higher triglycerides, apo E and apo CIII contents than controls, and abnormalities of VLDL and LDL with higher cholesterol, triglycerides, phospholipids and apo B contents than controls. Some of the risk factors of atherosclerosis were found in Alagille syndrome, namely high levels of plasma cholesterol, LDL cholesterol, apo B, apo B/apo AI. Treatment with cholestyramine resulted in a few modifications to the lipid profile, while lipoprotein-X and the decrease of LCAT activity persisted.
Atherosclerosis 1995 Jun
PMID:Lipoprotein pattern and plasma lecithin cholesterol acyl transferase activity in children with Alagille syndrome. 766 82

The changes in postprandial concentrations of five lipoparticles (LpC-III, LpC-III:B, LpC-IIInoB, LpA-I and LpA-I:A-II) were studied on 144 apparently healthy (71 male and 73 female) subjects during the 4 h following the ingestion of a 1.260 kJ milkshake. The influence of apo B signal peptide polymorphisms, apo E polymorphism, and other factors including age, gender, BMI, tobacco and alcohol consumption on the postprandial responses of lipoparticles was investigated. Apo-A-I-containing lipoparticles were not influenced during the 4 h following the test meal except for LpA-I:A-II, which decreased in women. LpA-I:A-II is the only particle that showed a gender-dependent change in postprandial concentration. Apo-CIII-containing lipoparticles showed significant postprandial variations. Particles containing both apo B and apo C-III (total LpC-III and LpC-III:B), mainly present in VLDL fraction, had significantly different postprandial responses among the genotypes of the apo B signal peptide polymorphism. Homozygotes for Del allele showed a decrease of LpC-III:B concentrations over the 4 h, whereas Ins/Ins homozygotes and Ins/Del heterozygotes had a peak in concentration at 2 h. The apo B signal peptide polymorphism explained 2.3% of the variance of LpCIII:B, whereas apo E polymorphism did not influence the postprandial concentrations of any lipoparticles.
Atherosclerosis 1995 Nov
PMID:Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles' responses. 857 28

There is a growing body of evidence supporting the roles of small, dense LDL and plasma triglyceride (TG), both features of the atherogenic lipoprotein phenotype, as risk factors for coronary heart disease. Although family studies and twin studies have demonstrated genetic influences on these risk factors, the specific genes involved remain to be determined definitively. The purpose of this study was to investigate genetic linkage between LDL size, TG, and related atherogenic lipoproteins and candidate genes known to be involved in lipid metabolism. The linkage analysis was based on a sample of 126 DZ women twin pairs, which avoids the potentially confounding effects of both age and gender, by use of a quantitative sib-pair linkage-analysis approach. Eight candidate genes were examined, including those for microsomal TG-transfer protein (MTP), hepatic lipase, hormone-sensitive lipase, apolipoprotein (apo) B, apo CIII, apo E, insulin receptor, and LDL receptor. The analysis suggested genetic linkage between markers for the apo B gene and LDL size, plasma levels of TG, of HDL cholesterol, and of apo B, all features of the atherogenic lipoprotein phenotype. Furthermore, evidence for linkage was maintained when the analysis was limited to women with a major LDL-subclass diameter >255 A, indicating that the apo B gene may influence LDL heterogeneity in the intermediate-to-large size range. In addition, linkage was found between the MTP gene and TG, among all the women. These findings add to the growing evidence for genetic influences on the atherogenic lipoprotein phenotype and its role in genetic susceptibility to atherosclerosis.
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PMID:Candidate-gene studies of the atherogenic lipoprotein phenotype: a sib-pair linkage analysis of DZ women twins. 946 19

The goal of the present study was to compare the allele frequency of four polymorphisms at the apo A-I C-III A-IV cluster gene locus-ApoA-I: XmnI and PstI; ApoC-III: SstI; ApoA-IV: XbaI-between male patients who had had a myocardial infarction (n= 614) and matched controls (n = 764). The association with a number of lipid lipoprotein, apolipoprotein and lipoprotein particle variables was also assessed. Patients and subjects were recruited in Belfast, Lille, Strasbourg and Toulouse in the framework of the ECTIM study. In the control group, the frequencies of the different polymorphic alleles were homogeneous among recruitment centres suggesting the absence of any European North to South gradient for these cluster polymorphisms. There was no evidence for a significant difference in allelic distribution between cases and controls suggesting that apo A-I, C-III, A-IV gene cluster polymorphisms do not explain MI survival in this sample of European men. There was no statistically significant association between apo A-I C-III A-IV cluster gene polymorphisms and lipid, lipoprotein, apolipoprotein, and lipoprotein particle levels. In conclusion, in the ECTIM study, the apo A-I, C-III, A-IV gene cluster polymorphism is associated with neither circulating plasma variables nor MI survival.
Atherosclerosis 1999 Jul
PMID:Lack of association between genetic variations of apo A-I-C-III-A-IV gene cluster and myocardial infarction in a sample of European male: ECTIM study. 1042 10

To investigate the relationship between parental history of myocardial infarction (MI), lipid traits and gene polymorphisms involved in lipid metabolism, we examined Dutch men and women, who were selected from a large population-based study. Subjects whose father (n=112), mother (n=115) or both parents (n=115) suffered from a premature MI presented with significantly higher apolipoprotein B (apo B) levels than subjects without a parental history (n=114). Genetic analyses revealed that the apo E4 isoform and the D9N mutation of lipoprotein lipase (LPL) were more frequent among subjects with a parental history (P< or =0.05). A similar trend was found for the LPL N291S mutation. In contrast, the LPL S447X mutation and polymorphisms at the cholesteryl ester transfer protein (TaqIB) and apo CIII (SstI) loci proved to be noninformative. Body mass index and lifestyle could not explain differences in apo B levels between parental history groups. In contrast, the apo E polymorphism and the LPL D9N mutation accounted for some, but not all, of the higher apo B levels in subjects with a parental history. Therefore, other genetic or lifestyle-related factors must be responsible for the increased levels of apo B in individuals with a family history of myocardial infarction.
Atherosclerosis 2001 Mar
PMID:Parental history of myocardial infarction: lipid traits, gene polymorphisms and lifestyle. 1122 36

Linkage and association of the apo AI-CIII-IV gene region to familial combined hyperlipidemia (FCHL) was reported previously, based on the presence of genetic variants in the apo CIII and apo AI gene. No data were available yet on the contribution of the apo A-IV locus. Two DNA variants in exon 3 of the apo A-IV gene, A (Thr)(347)T (Ser) and [CTGT](3-4) were characterized by sequencing the coding region of the apo A-IV gene and were analyzed in our Dutch FCHL cohort (30 probands, 159 affected relative, 317 unaffected relatives and 218 spouses). The genotype frequency of the A(347)T variant was different in probands and spouses. In probands no 2/2 carriers were found, resulting in a significant decreased frequency of the 2-allele (P<0.05). This was suggestive for a protective role of the presence of the serine (T) allele on the prevalence of FCHL. No difference in frequency distribution was found for the [CTGT](3-4) variant between the groups. Homozygous 4/4 carriers in spouses had a more favorable lipid profile (LDL-cholesterol and apo B, P<0.05). The absence of linkage disequilibrium of the A(347)T with other markers in the gene cluster, and the absence of linkage disequilibrium with [CTGT](3-4) marker and the MspI-AI marker in the apo A-I promoter showed that these two apo A-IV variants reside on different haplotypes from the apo A-I and apo C-III markers. This was illustrated by extensive haplotype analysis. The present data on the contribution of DNA variants in the apo A-IV gene support our previous observations that the apo AI-CIII-AIV gene cluster has a complex genetic contribution to FCHL both by conferring susceptibility and protection.
Atherosclerosis 2001 Oct
PMID:Two polymorphisms in the apo A-IV gene and familial combined hyperlipidemia. 1158 15

Fibrates regulates not only plasma lipid metabolism but vascular biology by activating nuclear receptor peroxisome proliferating activated alpha (PPAR alpha). Major effects on plasma lipid levels are lowering plasma triglyceride level and elevating plasma HDL cholesterol level, whereas its effect on plasma cholesterol level is moderate compared to HMG-CoA reductase inhibitor. As a mechanism for its effects on plasma lipid levels and atherosclerosis, recent studies reported that fibrates activates various genes involved in metabolism of remnants and HDL such as lipoprotein lipase, apo AI, apo AII, and apo CIII genes through the interaction with PPAR alpha, lowering atherogenic lipoproteins and elevating anti-atherogenic lipoproteins. Furthermore, fibrates may influence the process of atherosclerosis by modifying inflammatory process in vascular wall. Recent clinical studies demonstrated that fibrates significantly reduce cardiovascular events in patients with either hypertriglyceridemia or low HDL cholesterol level.
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PMID:[Fibrates]. 1203

Retention of apolipoprotein (apo)B and apoE-containing lipoproteins by extracellular vascular proteoglycans is critical in atherogenesis. Moreover, high circulating apoC-III levels are associated with increased atherosclerosis risk. To test whether apoC-III content of apoB-containing lipoproteins affects their ability to bind to the vascular proteoglycan biglycan, we evaluated the impact of apoC-III on the interaction of [(35)S]SO(4)-biglycan derived from cultured arterial smooth muscle cells with lipoproteins obtained from individuals across a spectrum of lipid concentrations. The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r = 0.78, P < 0.01), IDL (r = 0.67, P < 0.01), and LDL (r = 0.52, P < 0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apoC-III-containing lipoprotein particles in plasma by anti-apoC-III immunoaffinity chromatography. Since apoC-III does not bind biglycan directly, enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apoB and/or apoE become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apoC-III enrichment of LDL and VLDL did not increase binding. ApoC-III content may thus be a marker for lipoproteins characterized as having an increased ability to bind proteoglycans.
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PMID:ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan. 1240 96

Cardiovascular disease is a significant health problem affecting the adult population. Because atherosclerosis may begin in childhood, the aim of the present study was to identify biochemical markers for cardiovascular risk at an early stage of life. We studied 79 adolescents (48 girls and 31 boys) whose ages ranged from 13 to 17 years. A medical history (including pubertal stage by Tanner) was obtained from each subject. Anthropometric assessment was established by height, weight, body mass index (BMI), waist and hip circumferences, skinfolds, centrality index and obesity index. After a 12-h fast, basal blood glucose levels, total cholesterol, triglycerides, LDL-C and HDL-C were determined by enzymatic methods, mean basal insulin levels by radio immunoassays and apo A1, B, CIII by turbidimetric immunoassays. According to the BMI and taking 25 Kg/m2 as the cutoff value, 35% of the girls and 16% of the boys were obese. Eighty-five percent of the girls and 58% of the boys were hyperinsulinemic (basal insulin > 12 uU/ml). Circumferences, skinfolds, centrality and obesity index were higher (p < 0.05) in boys than in girls. In both, boys and girls, basal insulin levels were higher than the cutoff insulin value for our lab (>12 microU/ml), with the girls having higher insulin levels than the boys. Apo A1 was negatively associated with the obesity index and positively with HDL-C. Apo B was related to total cholesterol and LDL-C. Apo CIII was associated with basal insulin levels, triglycerides and VLDL-C. Our results suggest that apo CIII might be a good marker for higher insulin levels, insulin resistance and cardiovascular risk in adolescents.
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PMID:[Levels of apoproteins B, A1 and CIII as markers for cardiovascular risk in lean and obese adolescents]. 1505 56


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