Inheritance of combined hyperlipoproteinemia: Evidence for a new lipoprotein phenotype

Rose, Herbert G.; Kranz, Paul; Weinstock, Murray; Juliano, Joseph; Haft, Jacob I.

doi:10.1016/0002-9343(73)90218-0

Cited by 117 publications

(50 citation statements)

References 19 publications

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“…Familial combined hyperlipidemia (FCH) is a common heritable lipid disorder, in which affected individuals show elevations of plasma cholesterol, total triglycerides or both, with lipid phenotypes occurring within affected first-degree relatives, together with a high prevalence of pre mature cardiovascular disease [1][2][3]. Originally, it was supposed that FCH was caused by the vari able expression of a single autosomal dominant gene with primary action on plasma triglyceride levels and secondary on cholesterol levels [1].…”

Section: Introduction Of a Common Defect Assumed By Its Inheritedmentioning

confidence: 99%

Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia

et al. 1996

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The impact of apo E polymorphism on interindividual variation in plasma lipid, lipoprotein concentrations, and LDL subfraction profiles was studied in 201 well-defined patients (88 men and 103 women) with familial combined hyperlipidemia (FCH). When corrected for the concomitant influences of age, gender and obesity, the allelic variation in the apo E gene was shown to explain a statistically significant portion of the variability in lipid and (apo)lipoprotein concentrations. Carriers of the apo e2 allele exhibited a substantially higher plasma triglyceride concentration and a lower low density lipoprotein (LDL) cholesterol level, while subjects with the apo eA allele had significant higher total plasma cholesterol and LDL cholesterol levels. In line with this observation, our FCH population was characterized by an over-representation of the apo E4 allele as compared with a Dutch standard population (x 2 = 55.2, P < 0.0001). The contribution of apo E polymorphism to trait variability was different between sexes for plasma triglyceride, VLDL cholesterol, VLDL triglycerides, and high density lipoprotein (HDL) cholesterol levels. Apo E polymorphism had no impact on chemical composition of VLDL; for LDL particles the apo el allele was associated with a lower cholesterol to protein (C/P) ratio, whereas the opposite was true for the apo s4 allele. Despite the demonstrated impact of apo E polymorphism on plasma lipids and LDL chemical composition, in all phenotypic groups a dense LDL subfraction profile predominated. Thus, apo E polymorphism contributes to the lipid phenotypic expression in FCH, whereas further evidence was obtained that a dense LDL subfraction profile is an integral feature of FCH. 126 (1996) [313][314][315][316][317][318][319][320][321][322][323][324]

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Section: Introduction Of a Common Defect Assumed By Its Inheritedmentioning

confidence: 99%

Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia

et al. 1996

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“…Since its recognition in 1973, [1][2][3] it has been clinically defined by multiple lipid abnormalities that are exhibited by first-degree relatives within families. A prevalence of 1% among white populations makes it an important contributor to the burden of coronary artery disease.…”

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confidence: 99%

Quantitative Trait Loci for Apolipoprotein B, Cholesterol, and Triglycerides in Familial Combined Hyperlipidemia Pedigrees

Cantor

Bruin²,

Kono³

et al. 2004

ATVB

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Objective-Familial combined hyperlipidemia (FCHL) is a genetically complex lipid disorder that is diagnosed in families by combinations of increased cholesterol, triglycerides, and/or apolipoprotein B (apoB) levels in patients and their first-degree relatives. Identifying the predisposing genes promises to reveal the primary risk factors and susceptibility pathways and suggest methods of prevention and treatment. As with most genetically complex disorders, a clinical definition of disease may not be the most useful phenotype for finding the complement of predisposing genes, and the quantitative traits used to define the disorder can provide important information. This is a report of a quantitative trait loci (QTL) analysis of FCHL. Methods and Results-A full genome scan of 377 multi-allelic markers genotyped at Ϸ10 centimorgan (cM) intervals was conducted in 150 sibling pairs from 22 nuclear families in FCHL pedigrees. These data were analyzed by 2 multipoint QTL linkage methods using the nonparametric and Haseman-Elston procedures of the Genehunter software. Using a criterion of PϽ0.001 by the nonparametric analysis, we found evidence of 2 apoB QTL at 1p21-31 (PϽ0.000009) and 17p11-q21 (PϽ0.000009), a total serum cholesterol QTL at 12p13 (PϽ0.0001), and a serum triglycerides QTL at 4p15-16 (PϽ0.0002). Using the criterion of PϽ0.03 for at least 2 traits at the same locus, additional evidence for cholesterol (PϽ0.01) and a triglycerides PϽ0.02) was observed at 17p11-21, as well as suggestive evidence for apoB (PϽ0.02) and triglycerides (PϽ0.01) at 4q34-35, and cholesterol (PϽ0.01) and triglycerides (PϽ0.02) and a binary FCHL trait (lodϭ1.5) at 16p12-13. Conclusions-QTL analyses of the traits that define FCHL are effective for localizing disease-predisposing genes.

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“…[1][2][3][4][5] The diagnosis is based on clinical criteria such as the presence of "multiple type hyperlipidemia," [2][3][4][5] increased concentrations of plasma apoB, and a positive family history of premature coronary heart disease (CHD). The genetic basis of FCHL has not been elucidated, although several groups have provided evidence suggesting that different genes are involved in the pathogenesis of this disorder.…”

mentioning

confidence: 99%

Delayed and Exaggerated Postprandial Complement Component 3 Response in Familial Combined Hyperlipidemia

Meijssen

Dijk

Verseyden

et al. 2002

ATVB

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Inheritance of combined hyperlipoproteinemia: Evidence for a new lipoprotein phenotype

Cited by 117 publications

References 19 publications

Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia

Apolipoprotein E polymorphism influences lipid phenotypic expression, but not the low density lipoprotein subfraction distribution in familial combined hyperlipidemia

Quantitative Trait Loci for Apolipoprotein B, Cholesterol, and Triglycerides in Familial Combined Hyperlipidemia Pedigrees

Delayed and Exaggerated Postprandial Complement Component 3 Response in Familial Combined Hyperlipidemia

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