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)

Familial combined hyperlipidemia (FCHL) appears to be the most common, simply inherited hyperlipidemia strongly associated with coronary heart disease. In the family examined in this study, two of the siblings who met diagnostic criteria for FCHL had extensive clinical atherosclerosis before age 30, unusually premature for this form of hyperlipidemia. Lipoproteins and low-density lipoprotein (LDL) apolipoprotein (apo) B metabolism were characterized in these siblings in an attempt to gain insight into the cause of the rapid atherosclerosis in the two siblings so affected. LDL apo B production rates were very high in all three siblings (25 to 30 mg/kg/d), consistent with FCHL. beta-Very-low-density lipoprotein-beta (beta-VLDL) was present in the plasma of both siblings with accelerated atherosclerosis. The isoapolipoprotein E pattern in both of these siblings was E-3/E-2. In the third sibling, who was free of premature clinical atherosclerosis and lacked plasma beta-VLDL, the pattern was E-3/E-3. Thus, the heterozygote apo E-3/E-2 pattern may be related to the accumulation of beta-VLDL in persons with a very high apo B production rate. The abnormal accumulation of beta-VLDL may be one of the possible explanations for the rapid, premature atherosclerosis in the two siblings with FCHL in this kindred. Both male members in this kindred also had low levels of high-density lipoproteins, and thus may have had an additional risk of developing atherosclerosis due to this lipoprotein abnormality as well.
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PMID:Metabolism of apolipoprotein B in members of a family with accelerated atherosclerosis: influence of apolipoprotein E-3/E-2 pattern. 154 61

Familial combined hyperlipidemia (FCHL) is the most common genetic form of hyperlipidemia in which affected individuals manifest multiple lipoprotein phenotypes. Although the molecular defect is still unknown, several kinetic studies have demonstrated increased turnover rates of apolipoprotein B (apo B) in patients with FCHL, irrespective of their lipoprotein phenotype. Using 3 restriction fragment length polymorphisms (RFLPs) of the apo B gene (XbaI, MspI and EcoRI) we have investigated 33 families which fulfill the diagnostic criteria of FCHL. No significant difference in allele frequency was found between 33 unrelated individuals with FCHL and 107 normolipidemic controls. 3-RFLP haplotypes were constructed in each pedigree. A co-segregation analysis was performed in 7 informative families. In no family was co-segregation observed between the haplotype of the apo B gene and the phenotype of FCHL. These data are not compatible with the hypothesis that FCHL is caused by mutations of the apo B gene acting as a simple mendelian trait.
Atherosclerosis 1990 Jul
PMID:Genetic evidence from 7 families that the apolipoprotein B gene is not involved in familial combined hyperlipidemia. 197 79

Familial combined hyperlipidaemia (FCHL) is one of the major genetic causes of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals within a single family. Decreased lipoprotein lipase (LPL) activity has been found in some cases of FCHL. A recent study revealed a common mutation in the LPL gene, LPL(Asn291-->Ser), with a frequency of 9.3% in Dutch FCHL patients (Reymer et al,. Circulation, 90 (1994) I-998). This mutation was found in 3 out of 17 FCHL families. Extensive family studies were subsequently performed to determine the effect of this mutation on the phenotypic expression of FCHL. Using a pedigree-based maximum likelihood estimate, we demonstrated that the LPL(Asn291-->Ser) mutation significantly affects the levels of plasma and very low density lipoprotein (VLDL) triglycerides (2.03 +/- 0.21 vs. 1.14 +/- 0.13 and 1.21 +/- 0.16 vs. 0.62 +/- 0.09 mmol/l, carriers and non-carriers, respectively) and VLDL- and high density lipoprotein (HDL) cholesterol (0.83 +/- 0.10 vs. 0.38 +/- 0.06 and 1.02 +/- 0.08 vs. 1.29 +/- 0.05 mmol l, carriers and non-carriers, respectively), but not those of plasma and low density lipoprotein (LDL) cholesterol. These findings indicate that the LPL(Asn291-->Ser) mutation is associated with elevated lipid levels, indicating it may be one of the genetic factors predisposing to FCHL in the families studied.
Atherosclerosis 1996 Jan 26
PMID:The lipoprotein lipase (Asn291-->Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia. 880 93

Familial combined hyperlipidemia (FCHL) is a common inherited lipid disorder, affecting 1 to 2 percent of the population in Westernized societies. Individuals with FCHL have large quantities of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) and develop premature coronary heart disease. A mouse model displaying some of the features of FCHL was created by crossing mice carrying the human apolipoprotein C-III (APOC3) transgene with mice deficient in the LDL receptor. A synergistic interaction between the apolipoprotein C-III and the LDL receptor defects produced large quantities of VLDL and LDL and enhanced the development of atherosclerosis. This mouse model may provide clues to the origin of human FCHL.
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PMID:A mouse model with features of familial combined hyperlipidemia. 899 37

Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid disorders. Resistance of adipocytes to the effects of acylation stimulating protein (ASP) may contribute to ineffective triglyceride synthesis and thereby prolonged postprandial lipemia and increased fatty acid flux to the liver seen in FCHL patients. Interestingly, ASP is identical to C3a-desArg, fragment of the third component of complement. We examined the relationships between serum levels of complement components C3 and C4 and markers of lipid and glucose metabolism in 11 large FCHL families (n = 53). Median serum C3 levels were 38% higher in affected compared to non-affected male FCHL family members (1.90 g/l vs. 1.38, P = 0.0027). The strongest correlations were observed between serum complement C3 and apolipoprotein B levels, reaching 0.77 in males. These relations were not confounded by obesity or impaired glucose tolerance. In conclusion, serum levels of the main complement components C3 and C4 correlated significantly with serum lipid levels. Further studies are needed to clarify the importance of disturbances in the complement system on the pathogenesis of FCHL and other lipid disorders.
Atherosclerosis 1997 Mar 21
PMID:Serum complement and familial combined hyperlipidemia. 962 89

Familial combined hyperlipidaemia (FCHL) is one of the most common hereditary disorders predisposing to early coronary death. The affected family members have elevations of serum total cholesterol, triglycerides or both. Despite intensive research efforts the genetic and metabolic defects underlying this complex disorder are still unknown. To dissect the metabolism and genetics of FCHL the phenotype of an individual must be precisely defined. We assessed the influence of different diagnostic criteria on the phenotype definition and studied factors affecting the phenotype expression in 16 large Finnish families (n = 255) with FCHL. The fractile cut-points used to define abnormal lipid values had a profound influence on the diagnosis of FCHL. If the 90th percentile cut-point was used, approximately 45% of the family members were affected, in concord with the presumed dominant mode of transmission for FCHL. If the 95th percentile was used only 22% of study subjects were affected. To characterize the metabolic differences or similarities between the different lipid phenotypes, we determined very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) particles separated by ultracentrifugation. In linkage analysis no single ultracentrifugation variable could discriminate reliably affected family members from non-affected family members. Our data emphasizes the need for re-evaluation of FCHL diagnostic criteria. Preferably, the diagnosis should be based on a single, reliable metabolic marker.
Atherosclerosis 1997 Sep
PMID:Phenotype expression in familial combined hyperlipidemia. 929 85

Familial combined hyperlipidemia is a common inherited disorder characterized by a hepatic overproduction of apo B particles and an elevated risk for the development of atherosclerosis. LDL particles are smaller and denser and are more prone to oxidation. The exact pathogenesis of familial combined hyperlipidemia is unclear at present. Treatment should aim to reduce the synthesis of atherogenic lipoproteins and to increase the clearance of triglyceride-rich lipoproteins.
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PMID:[Familial combined hyperlipidemia]. 943 74

Familial combined hyperlipidemia (FCHL) is a frequent cause of premature coronary artery disease. Affected family members are characterized by different combinations of elevated cholesterol and/or triglyceride levels. A reduction in lipoprotein lipase (LPL) activity has been observed in a subgroup of FCHL patients. Recently, we have demonstrated an increased frequency of mutations in the LPL gene in Dutch FCHL patients compared to normolipidemic controls. In the present study, we have applied a pedigree-based maximum likelihood method to study the effect of LPL mutations on the phenotypic expression of FCHL in families. In 40 FCHL probandi, three different previously reported mutations in the LPL gene were identified resulting in amino acid changes, D9N, N291S, and S447X. The D9N mutation in exon 2 appeared to be in strong linkage disequilibrium with a T-->G substitution at position -93 in the promoter region of the LPL gene. We present data that the -93T-->G/D9N haplotype is associated with significantly higher levels of LDL and VLDL cholesterol, and VLDL triglycerides. Interestingly, the effect was only observed in male carriers. In line with our previous observations, these results further sustain that the LPL gene is a susceptibility gene for dyslipidemia which explains part of the variability in the phenotype observed among FCHL family members.
Atherosclerosis 1998 May
PMID:Gender-related association between the -93T-->G/D9N haplotype of the lipoprotein lipase gene and elevated lipid levels in familial combined hyperlipidemia. 967 74

INSUFFICIENT PROGRESS: The treatment of hyperlipidemia leads to a reduced risk of coronary disease. This has been displayed notably since clinical trials have used statins. However, despite these treatments, a risk of coronary ischemia remains, which is not insignificant. There are several causes of this persistent risk which need to be analyzed. THE QUALITATIVE ASPECT OF LOW DENSITY LIPOPROTEINS: LDL are heterogeneous. This is displayed by a distribution of sizes varying from one subject to another. The predominance of small LDL is frequently found in coronary subjects detected during prospective or retrospective studies. The atherogenicity of small LDL can be explained by their physico-chemical characteristics. A remarkable fact is the predominance of small LDL in subjects with a mixed hyperlipidemia presenting a high risk of atherosclerosis. THE EFFECTS OF HYPOLIPIDEMIANTS: Statins greatly decrease LDL-cholesterol without changing LDL distribution according to size. Conversely, fibrates noticeably modify LDL distribution, reducing the percentage of small LDL. A PROPOSAL FOR THE TREATMENT OF SUBJECTS SUFFERING FROM MIXED HYPERLIPIDEMIA: If the concentration of LDL (reflected by LDL-cholesterol) and LDL distribution are two risk factors of atherosclerosis, hypolipidemic treatment should aim to act upon these two parameters, but no commercialized hypolipidemiant is effective enough as fas as they are both concerned. Therefore the combination of two hypolipidemiants, a statin and a fibrate, each having a predominant effect on one of the two factors, could be particularly effective in reducing coronary risk. This therapeutic association is effective on classic lipid parameters, does not entail more side effects than a monotherapy, and is not precluded by the RMO when there is a high vascular risk, which is often the case in mixed hyperlipidemia.
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PMID:[Is combined statin and fibrate therapy indicated in the management of mixed hyperlipidemia?]. 976 13

Familial combined hyperlipidemia (FCHL) is a heritable lipid disorder characterized by multiple lipoprotein phenotypes within a single family. Previously, we have shown an increased incidence of mutations in the LPL gene which was associated with elevated levels of very low density lipoprotein (VLDL) and decreased levels of high density lipoprotein among the families studied. Now, we report the results of our study on the hepatic lipase gene. We found the HL V73M variant to be present in four FCHL families. By means of a pedigree-based maximum log-likelihood method we analyzed the effect of this variant on the lipid levels in these families. Carriers of the HL V73M variant revealed significantly higher levels of total cholesterol (P < 0.01) and apoB (P <0.01). These findings show that the HL V73M mutant explains another part of the variability in the phenotype observed among FCHL family members, compared with mutations in the LPL gene. Family analysis shows that in these FCHL families, carriers of mutations in the LPL or HL genes have an increased risk for FCHL compared with their non-carrier relatives.
Atherosclerosis 2000 Aug
PMID:The V73M mutation in the hepatic lipase gene is associated with elevated cholesterol levels in four Dutch pedigrees with familial combined hyperlipidemia. 1092 21


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