Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FH”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1992

Angiographic and pathological studies on regression of coronary atherosclerosis of FH patients who received LDL-apheresis treatment.

We report on the most recent data confirming the angiographic and pathological efficacy of LDL-apheresis for coronary atherosclerosis of a familial hypercholesterolemia (FH) patient using collected data of a large number of cases and especially of one autopsy case. Changes in coronary artery stenosis have been assessed angiographically in 37 FH patients in the LDL-Apheresis Regression Study (LARS) group of 13 institutions in Japan. Definite regression was observed in 21 segments by visual and computer analysis. Fourteen of 37 patients (37.8%) who had received LDL-apheresis treatment in combination with cholesterol-lowering drugs had at least one regressed segment without any progressed segment. We pathologically examined at autopsy the coronary arteries in one FH patient who had received long-term LDL-apheresis therapy before death. The results revealed the process of scarring of atheromatous plaque, suggesting pathological regression correlated with the angiographic regression shown in serial angiograms taken during LDL-apheresis treatment. It was further suggested that the formation of an eccentric thickened wall lesion rich in collagen fiber prevented atheromatous plaque from tearing off. Such tearing off might lead to an acute coronary event. Aggressive cholesterol-lowering therapy based on LDL-apheresis can induce both angiographic and pathological regression in coronary atherosclerosis of FH patients.

Adult↗
PubMed2004

Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma.

BACKGROUND: Overexpression of the hypoxia inducible factor 1 (HIF-1) and HIF-2 transcription factors and the consequent upregulation of hypoxia inducible mRNAs is a feature of many human cancers and may be unrelated to tissue hypoxia. Thus, the VHL (von Hippel-Lindau) tumour suppressor gene (TSG) regulates HIF-1 and HIF-2 expression in normoxia by targeting the alpha subunits for ubiquitination and proteolysis. Inactivation of the VHL TSG in VHL tumours and in sporadic clear cell renal cell carcinoma (RCC) results in overexpression of HIF-1 and HIF-2. However, RCC without VHL inactivation may demonstrate HIF upregulation, suggesting that VHL independent pathways for HIF activation also exist. In RCC, three candidate HIF activating genes exist-FIH-1 (factor inhibiting HIF), SDHB, and FH-which may be dependent or independent of VHL inactivation. AIMS: To investigate FIH-1, SDHB, and FH for somatic mutations in sporadic RCC. METHODS: Gene mutation was analysed in primary RCCs (clear cell RCCs, papillary RCCs, and oncocytomas) and RCC cell lines. SDHB mutation analysis was performed by denaturing high performance liquid chromatography followed by direct sequencing of aberrant PCR products. FH and FIH-1 mutation analysis were performed by single stranded conformational polymorphism and direct sequencing of PCR products. RESULTS: No mutations were identified in the three genes investigated. CONCLUSIONS: There was no evidence to suggest that somatic mutations occur in the FH, FIH-1, or SDHB TSGs in sporadic RCCs.

Base Sequence↗
PubMed1995

Characterization of a splice-site mutation in the gene for the LDL receptor associated with an unpredictably severe clinical phenotype in English patients with heterozygous FH.

We have identified a substitution of G to A in the first base pair of intron 3 in the LDL receptor gene of an English heterozygous familial hypercholesterolemia (FH) patient. Reverse transcription, amplification, and nucleotide sequencing of the LDL receptor mRNA from mononuclear blood cells showed both the normal mRNA and one that lacked the nucleotides encoded by exon 3, which codes for repeat 2 of the ligand-binding domain. The same mutant allele was identified in 2/200 unrelated FH patients from the London area and 4/77 from Manchester. Immunoblotting of cultured lymphoblasts from the index patient revealed the normal receptor protein and smaller amounts of a receptor protein with electrophoretic mobility consistent with a deletion of the 41 amino acid residues encoded by exon 3. Normal amounts of a similar protein were observed when the mutant cDNA was expressed in heterologous cells; this protein showed reduced binding affinity for LDL but bound apoprotein E-containing lipoproteins normally. Despite these and other observations that repeat 2 of the binding domain is relatively unimportant for receptor function in vitro, carriers of this allele exhibit a severe clinical phenotype, typical of FH. Thus, the relationship between genotype and phenotype in heterozygous FH is not always predictable.

Adult↗
PubMed1989

Finnish type of low density lipoprotein receptor gene mutation (FH-Helsinki) deletes exons encoding the carboxy-terminal part of the receptor and creates an internalization-defective phenotype.

A specific type of gene mutation affecting the LDL receptor has been found in many Finnish patients with familial hypercholesterolemia (FH). The mutant allele is characterized by a 9.5-kb deletion extending from intron 15 to exon 18. Molecular cloning and sequencing of a cDNA segment corresponding to the deleted allele indicated that the mutant receptor differs radically from the normal one because of loss of the domains encoded by exons 16, 17, and 18. The carboxy-terminal portion of the normal receptor, comprising the amino acids 750-839, has been replaced by an unrelated stretch of 55 amino acids. The mutant allele was found to occur in 23 (50%) of 46 unrelated FH patients with an established functional defect in the LDL receptor. In cultured fibroblasts from the FH patients with the 9.5-kb deletion, both receptor-mediated binding and internalization of 125I-LDL were lower than normal, the former, on average, by 25%, and the latter, on average, by 50%. This combined functional defect probably results from both impaired attachment and impaired internalization of the mutated receptor. It remains to be investigated whether this Finnish type of LDL receptor gene mutation, here designated FH-Helsinki, occurs in other ethnic groups.

Adult↗
PubMed1996

Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom.

Mutations in the gene for the low density lipoprotein (LDL) receptor have been identified in 15 patients with homozygous familial hypercholesterolemia (FH). Five patients are homozygous at the LDL-receptor locus; their mutant alleles include Glu387Lys and Pro664Leu in patients of Asian-Indian descent, Cys292Stop in a Greek Cypriot, Cys281Trp in a Turkish patient, and Gln 540Stop in a West Indian. The other 10 patients (9 of apparently British ancestry) are compound heterozygotes. Mutations have been identified in 18 of 20 possible alleles, including Glu80Lys (2 patients), Pro664Leu (3 patients), Asp69Gly, Cys176Arg, Cys227Tyr, Ser265Arg, Asp280Ala, Asp283Glu, Arg329Pro, Asp461Asn, Leu578Ser, a single bp deletion in exon 15, a 21 bp duplication of codons 200-206 and two large deletions. The seven mutations underlined above have not been described previously. The two uncharacterized mutant alleles fail to produce detectable amounts of mRNA. LDL-receptor activity in cultured cells from 13 of the 15 homozygous patients varied from undetectable to about 30% of normal, but there was no correlation between LDL-receptor activity and the untreated plasma cholesterol concentration in these patients. When genomic DNA from 295 patients with a clinical diagnosis of FH was screened for 29 mutations found in these and other FH patients of British ancestry, most were identified in only one or a few individuals. Four patients heterozygous for the Asp461Asn allele showed a wide range of clinical manifestations. These observations confirm the striking heterogeneity underlying FH in most populations and demonstrate the variability in phenotype between patients with the same mutation.

Adolescent↗
PubMed1998

Effects of a 9.6-kb deletion of the LDL receptor gene (FH Helsinki) on structure and levels of mRNA.

FH Helsinki is a deletion of the low-density lipoprotein receptor (LDLR) gene that deletes 9.6 kb from intron 15 to exon 18. Screening for mutant transcripts by Northern blot analysis from a patient heterozygous for FH Helsinki revealed two mutant transcripts. One was a transcript where the proximal part of intron 15 was retained in mRNA. The second was a transcript where exon 15 was spliced to nucleotide 4186 of exon 18. Thus, this transcript was generated using the normal donor splice site in intron 15, and a cryptic AG acceptor splice site in exon 18. Translation of the two mutant transcripts is predicted to give nonfunctional proteins, as both the membrane-spanning domain and the cytoplasmic domain of the receptor are deleted. Scanning of the autoradiograms showed that the amounts of each of the two mutant transcripts were approximately 10 times higher than that of the normal transcript in our heterozygous patient. The finding of higher levels of mutant transcripts was confirmed by an allele-specific transcript quantitation method, in which the amount of the two mutant transcripts together was approximately 5 times higher than the amount of the normal transcript. Deletion of destabilizing elements (AU-rich elements) by FH Helsinki are proposed to cause the increased levels of mutant transcripts.

Base Sequence↗
PubMed1994

Hypocholesterolemic effects of mixture Da Huai on experimental rats and treatment of a homozygous FH child.

This study observes the hypocholesterolemic effects of Mixture Da Huai--a drug of enhancing monocyte macrophage system--on experimental rats, and the treatment of a homozygous familial hypercholesterolemia (FH) child. The results show that TC, VLDL-C and LDL-C in Mixture Da Huai group were significantly reduced and HDL-C was significantly increased. Fractional clearance rates for 125I-GLC-LDL, and the 125I-GLD-LDL uptake of rat peritoneal macrophages were significantly increased. Excretions of total sterol and acidic sterol in feces were also increased. After treatment for 3 months, serum TC and LDL-C of a homozygous FH child were significantly decreased. Tendon and cutaneous xanthomas were limited. This study indicates that by promoting the monocyte macrophage system to degrade LDL, a promising prevention and treatment of hypercholesterolemia and atherosclerosis might be provided, especially in the treatment of homozygous FH.

Animals↗
PubMed1995

Response of 3-hydroxy-3-methylglutaryl CoA reductase to l-triiodothyronine in cultured fibroblasts from FH homozygotes.

The effect of l-triiodothyronine on 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase activity was measured in cultured skin fibroblasts from patients with homozygous familial hypercholesterolemia (FH). The tested strains were obtained from 13 receptor-negative and 6 receptor-defective type homozygotes and 3 heterozygotes. Eleven out of 19 strains of cultured fibroblasts from FH homozygotes demonstrated high levels of the HMG CoA reductase activity when l-triiodothyronine was present in the culture medium. All the 11 strains that responded to l-triiodothyronine were the receptor-negative type in which the binding of LDL on the cell surface was completely lacking. Two receptor-negative type strains showed no response to the addition of l-triiodothyronine. In these strains, partially active receptors were synthesized and rapidly degraded. The effect of l-triiodothyronine on HMG CoA reductase was abolished by cycloheximide, and not by actinomycin D. Furthermore, the effect was abolished by the pre-loading of the cells with free cholesterol. The results indicate that the effect of l-triiodothyronine on HMG CoA reductase activity was a post-transcriptional event, required de novo protein synthesis, and was successful only when cholesterol was depleted from the cells. The difference in the responsiveness of HMG CoA reductase activity to l-triiodothyronine treatment can be utilized to judge the state of impairment of LDL-receptors in the FH homozygote from the viewpoint of ability to incorporate cholesterol into the cells.

Cells, Cultured↗
PubMed2004

Genetic screening of patients with familial hypercholesterolaemia (FH): a New Zealand perspective.

Using denaturing high performance liquid chromatography (DHPLC) to screen the LDL receptor gene of people with familial hypercholesterolaemia (FH) in Christchurch, New Zealand, we have identified mutations in 65 patients (44 different mutations, of which 15 are novel). We also test family members of probands for the mutation identified in their relative, allowing diagnosis of affected children and those without classical FH symptoms. This screening programme is helpful to clinicians and benefits FH patients and their families, and has provided us with a pool of LDL receptor variants on which to base research into this disease.

Chromatography, High Pressure Liquid↗
PubMed2005

Non-cholesterol sterols in serum, lipoproteins, and red cells in statin-treated FH subjects off and on plant stanol and sterol ester spreads.

BACKGROUND: Serum plant sterol levels are increased by consumption of statins and dietary plant sterols, and decreased by dietary plant stanols, but little is known about combination therapy of statin and plant sterols. METHODS: We measured plant sterols in serum, lipoproteins, and red cells in subjects with familial hypercholesterolemia (FH) (n=18) treated with variable doses of statins off and on plant stanol (STA) and sterol ester (STE) spreads. RESULTS: STA and STE spreads lowered LDL cholesterol approximately 15%. Plant sterols were decreased in serum, lipoproteins, and red cells by approximately 25% with STA and increased from 37% to 80% with STE, especially with high statin doses. The changes in serum were related to those in red cells. The baseline levels of serum plant sterols were negatively (r-range -0.639 to -0.935) and positively (r-range 0.526 to 0.598) correlated with the respective changes evoked by the STA and STE spreads. CONCLUSIONS: STE reduces LDL cholesterol, but increases serum, lipoprotein, and red cell plant sterol levels in statin-treated FH subjects, while all the respective values are decreased with STA. Recent predictions that elevated serum plant sterols pose an increased coronary risk suggest that increases of serum plant sterol levels should be avoided, especially in atherosclerosis-prone individuals, such as subjects with FH.

Adult↗
PubMed2001

Atorvastatin improves blood rheology in patients with familial hypercholesterolemia (FH) on long-term LDL apheresis treatment.

To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH) on regular LDL apheresis, we prospectively studied the rheological variables fibrinogen, plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit and platelet aggregation in 12 patients (two homozygous, ten heterozygous) before and during treatment with atorvastatin. Baseline values of red cell aggregation and whole blood viscosity were increased in FH patients on regular LDL apheresis compared with healthy controls (P<0.05), whereas fibrinogen, plasma viscosity and hematocrit were similar in the two groups. Treatment with atorvastatin reduced red cell aggregation (P<0.01), whole blood viscosity (P<0.01), plasma viscosity (P<0.01) and platelet aggregation (P<0.05), but caused a slight increase in plasma fibrinogen (by 5%; P<0.01). Our findings suggest that atorvastatin improves blood rheology in patients with FH on regular LDL-apheresis. This improvement in blood flow properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.

Adult↗
PubMed2006

Transition-state energy and geometry, exothermicity, and van der Waals wells on the F + H2 --> FH + H ground-state surface calculated at the r12-ACPF-2 level.

Explicitly correlated averaged coupled-pair functional methods have been used to compute the ground-state Born-Oppenheimer potential energy surface for the F + HH' --> FH + H' reaction at the F + HH' and FH + H' asymptotes, the F...HH', and FH...H van der Waals wells, the reaction transition state, and at points along the intrinsic reaction coordinate connecting all of these stationary points. To these energies, corrections for spin-orbit coupling and scalar relativistic effects were added to produce total electronic energies whose accuracy is demonstrated to be very high (e.g., 0.1 kcal mol(-1)). The final data are used to refine the two-body parts of the currently best three-dimensional potential energy surface for this reaction, to predict several spectroscopic parameters of the species involved, and to offer accurate estimates of the title reaction's exothermicity (32.0 kcal mol(-1)) and activation barrier (1.8 kcal mol(-1)) as well as the geometry of the transition state.

Journal Article↗
PubMed2001

Large rearrangements of the LDL receptor gene and lipid profile in a FH Spanish population.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density lipoprotein receptor (LDLR) gene. To date, there has not been a systematic survey of the frequency of gross mutations in the LDLR gene in the Spanish population. The objective of our study was to investigate large rearrangements in the Spanish FH population and the relation between the kind of large rearrangement and the phenotype in carrier families. MATERIALS AND METHODS: The LDLR gene was screened to detect major rearrangements in a sample of 89 probands. Southern blot, long polymerase chain reaction (PCR), reverse transcription (RT) -PCR and DNA sequencing were used to detect and characterize the mutations. RESULTS: Five large rearrangements were found in six probands. Two mutations were due to duplications of internal regions of the gene, whereas the rest were caused by partial deletions, which eliminated the promoter region in two cases. The internal rearrangements, two duplications and one deletion, were apparently caused by recombination between ALU sequences and the study of their mRNA indicated that the reading frame was maintained. The analysis of the lipid profile between patients with similar characteristics (age, sex, body mass index, etc.) but carrying mutations that either eliminated the promoter region or produced internal rearrangements showed significant differences (total cholesterol: 366.6 +/- 81.8 vs. 304.6 +/- 25.1 P = 0.023, and LDL cholesterol: 317.7 +/- 65.1 vs. 249.2 +/- 27.4 P = 0.003). CONCLUSIONS: The frequency of large mutations in a Spanish FH sample was close to 7% and at least four of the mutations found had not been described in other populations. Mutations that eliminate the promoter region originate more severe hypercholesterolemia than defective mutations, which suggests that the absence of the promoter region and transcription of the LDLR gene is worse compensated than the synthesis of a defective LDL receptor.

Adult↗
PubMed2005

Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.

The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C and -D), act as tumour suppressors. Germline mutations in FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL). In this study, we have shown that FH-deficient cells and tumours accumulate fumarate and, to a lesser extent, succinate. SDH-deficient tumours principally accumulate succinate. In situ analyses showed that these tumours also have over-expression of hypoxia-inducible factor 1alpha (HIF1alpha), activation of HIF1alphatargets (such as vascular endothelial growth factor) and high microvessel density. We found no evidence of increased reactive oxygen species in our cells. Our data provide in vivo evidence to support the hypothesis that increased succinate and/or fumarate causes stabilization of HIF1alpha a plausible mechanism, inhibition of HIF prolyl hydroxylases, has previously been suggested by in vitro studies. The basic mechanism of tumorigenesis in HPGL and HLRCC is likely to be pseudo-hypoxic drive, just as it is in von Hippel-Lindau syndrome.

Carcinoma, Renal Cell↗
PubMed2004

FH clinical phenotype in Greek patients with LDL-R defective vs. negative mutations.

BACKGROUND: Familial hypercholesterolaemia (FH) is caused by mutations in the low-density lipoprotein receptor gene and the gene encoding apolipoprotein B-100, affecting one in 500 individuals. METHODS: One hundred and eighty-three Greek FH patients were screened for mutations on the LDLR and ApoB genes. RESULTS: We identified mutations in 67 probands and 11 relatives. Sixteen mutations located in eight different exons and the promoter of the LDLR were discovered. Among them 10 were missense mutations (C6W, S265R, A370T, Q363P, D365E, V408M, A410T, A517T, G528D, G571E), two were nonsense mutations (Q363X and C660X), three were splice defects (2140 + 5G-->A and 2140 + 9C-->T, 1706 - 10G-->A), and one was a nucleotide substitution (- 45delT) on the promoter. None of the subjects carried any apoB mutation. The detection rate of mutations in this study was 43%. From the above mutations, A410T, A519T and the splice site defects 2140 + 9C-->T were detected for the first time in the Greek population. Among them V408M, G528D, C6W and S265R account for 73% of heterozygous FH probands. V408M mutation is more common in Central West, while C6W is more common in Central East. Separating the patients into two groups (receptor defective and receptor negative) we found that the receptor negative group had higher levels of total cholesterol, low-density lipoprotein cholesterol and higher prevalence of tendon xanthomas compared with the receptor-defective group. DISCUSSION: The homogenous molecular basis of familial hypercholesterolaemia in Greece facilitates the application of a DNA diagnostic strategy based on the origin of the patient. The early mutation analysis would add valuable information on the severity of the disease.

Apolipoprotein B-100↗
PubMed1995

The proline-rich P65 protein of Mycoplasma pneumoniae is a component of the Triton X-100-insoluble fraction and exhibits size polymorphism in the strains M129 and FH.

Previously, we described the identification of a novel Mycoplasma pneumoniae M129 protein, named P65 because of its apparent molecular mass of 65 kDa estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (T. Proft and R. Herrmann, Mol. Microbiol. 13:337-348, 1994). DNA sequence analysis of the P65 open reading frame (orfp65), however, revealed an ORF encoding a protein with a molecular weight of 47,034. This discrepancy can be explained by the unusual amino acid composition of this protein. According to the deduced amino acid sequence, the N-terminal half of P65 contains several penta- and hexapeptides (DPNAY and DPNQAY) forming a proline-rich acidic domain. Secondary-structure predictions indicated beta-sheets and turns within that region, suggesting an extended and rigid conformation. Near the C terminus of P65 the tripeptide Arg-Gly-Asp (RGD) was found. This motif is known to play an important role in binding of extracellular matrix proteins to integrins. P65 could be located exclusively to the Triton X-100-insoluble cell fraction. The results of immunofluorescence microscopy and of immunoadsorption experiments indicated that P65 carries surface-exposed regions. Mild treatment of whole cells with proteases resulted in cleavage of a limited amount of P65 molecules, suggesting either that only a small percentage of P65 molecules are exposed on the surface or that protease cleavage is hampered by a compact protein conformation or by binding of an unknown component to P65. P65 exhibits size polymorphism in M. pneumoniae M129 and FH. This is caused by an intragenetic duplication of a 54-bp sequence within the FH orfp65. As a consequence, the number of DPNAY pentapeptides increased from 9 to 12 repeats in the FH strain.

Amino Acid Sequence↗
PubMed2005

Efficacy of colestimide coadministered with atorvastatin in japanese patients with heterozygous familial hypercholesterolemia (FH).

BACKGROUND: Colestimide, a 2-methylimidazole-epichlorohydrin polymer, is a new bile-acid-sequestering resin, that is 4-fold as powerful at lowering low-density lipoprotein cholesterol (LDL-C) as the conventional resin (cholestyramine). Moreover, colestimide has excellent patient compliance because it is available in tablet form. METHODS AND RESULTS: The clinical efficacy of colestimide coadministered with atorvastatin on lipid and apolipoprotein concentrations was examined in 15 patients (M/F=10/5, mean+/-SE age=54+/-9 years) with heterozygous familial hypercholesterolemia (FH). After a period of wash-out of any lipid-lowering drugs, atorvastatin (20-40 mg) was administered to patients for at least 8 weeks, and then 3 g of colestimide was administered for a further 8 weeks. Total and LDL-C significantly (<0.0001) decreased by 35% from 361 to 233 mg/dl and 41% from 274 to 161 mg/dl, respectively. Addition of colestimide caused a further significant 12% and 20% reduction, respectively, from the initial values to 205 and 129 mg/dl, respectively. Colestimide was also effective in reducing serum LDL-C concentrations in heterozygous FH patients with hypertriglyceridemia (triglycerides>or=150 mg/dl). CONCLUSIONS: When monotherapy with atorvastatin is insufficient to treat severely hypercholesterolemic patients, such as those with heterozygous FH, colestimide acts to reinforce the action of statins.

Anion Exchange Resins↗
PubMed1999

[Evaluation of a newly discovered LDL receptor mutation (exon 10, GAC>AAC, D271N, "FH Graz-1") in familial hypercholesterolemia-- a familystudy].

Heterozygous familial hypercholesterolemia (FH, prevalence 1:500) is a major cause of early atherosclerotic disease. Little is known about possible co-factors influencing individual patient's risk. We investigated this question in a large family carrying a new LDL-receptor-mutation. Genetic analysis of all exons of the LDL-receptor gene in the index case using polymerase chain reaction (PCR) and Denaturing Gradient Gel Electrophoresis (DGGE) revealed a previously unknown mutation in exon 10 (GAC > ACC, D471N, "FH Graz-1"). Investigation of 21 family members (15 females, 6 males), aged 17 to 86 years, revealed 9 female and 4 male carriers of the mutation. 7 female carriers aged 17 to 58 years show no clinical signs of macrovascular disease. An 86-year old female patient, who was asymptomatic until 85, recently suffered a transient cerebral ischemic attack. All these females were normotensive. The only hypertensive 76-year old patient (ex-smoker with a history of 15 pack years) suffers from angina pectoris. 2 male carriers of the mutation (32 and 38 years old) are asymptomatic. A 65-year old patient suffers from cardiovascular disease. A 49-year old patient had a coronary artery bypass graft after a myocardial infarction at the age of 37. Additionally he has a history of bilateral thrombendarterectomy of the carotid arteries and suffers from bilateral peripheral artery disease. This patient also carries the apoE-genotype 4/3, which might be responsible for his poor response to stain therapy, and needs extracorporal lipid elimination (LDL-C > 200 mg/dl under drug therapy). Both of his daughters are homozygous for the apoE-allele 3 and and responded well to stain therapy. Genetic analysis in patients with FH assures diagnosis, but is not sufficient to determine the individual patient's risk. A precise clinical examination remains the gold standard for individual risk evaluation.

Adolescent↗