Variation of Apolipoprotein-B Gene Is Associated With Obesity, High Blood Cholesterol Levels, and Increased Risk of Coronary Heart Disease

Rajput-Williams, J.; Wallis, S.; Yarnell, John; Bell, Graeme I.; Knott, T J; Sweetnam, P. M.; Cox, Nancy J.; Miller, N. E.; Scott, James

doi:10.1016/s0140-6736(88)90930-0

Cited by 111 publications

(34 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, APOB is critical for the synthesis, transport, and catabolism of TG-rich and cholesterol-rich lipoproteins in the intestine and liver ( 11,12 ). Polymorphisms in the APOB gene have been associated with the variability of serum cholesterol levels and coronary atherosclerosis in some populations ( 13 ) but not all ( 14 ). No studies have examined the role of APOB genetic variants in relation to the lipid-lowering effects of fenofi brate.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study

Wojczynski

Gao

Borecki³

et al. 2010

Journal of Lipid Research

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study

Wojczynski

Gao

Borecki³

et al. 2010

Journal of Lipid Research

View full text Add to dashboard Cite

“…All persons were genotyped for the following seven polymorphic alleles in or near the apo B gene: a 9-bp insertion/ deletion polymorphism in the signal peptide coding region (Ins/Del), 11 aPvu II restriction fragment length polymorphism (RFLP) in intron 4, 12 an Alu I RFLP in exon 14, 12 an Xba I RFLP in exon 26, an Msp I RFLP in exon 26, an EcoRl RFLP in exon 29, 13 and a 3' variable number of tandem repeats (VNTR) polymorphism. 1415 All polymorphic markers were determined after PCR amplification by restriction enzyme digestion and/or size separation by gel electrophoresis as described in Hansen et al 16 and Ludwig and McCarthy.…”

Section: Haplotype Markersmentioning

confidence: 99%

Characteristics of 46 heterozygous carriers and 57 unaffected relatives in five Danish families with familial defective apolipoprotein B-100.

Hansen

Meinertz

Jensen

et al. 1994

Arterioscler Thromb

View full text Add to dashboard Cite

Plasma concentrations of cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein(a) (Lp[a]) in 46 persons heterozygous for the apo B-3500 mutation causing familial defective apo B-100 (FDB) were compared with those in 57 non-FDB relatives. FDB patients had 50% to 70% higher mean concentrations of cholesterol, LDL cholesterol, and apo B than non-FDB relatives (P50 years old had atherosclerotic disease. In contrast, all 18 non-FDB relatives >50 years old were apparently healthy. A total of 8 FDB patients with atherosclerotic disease had 36% higher cholesterol concentrations, 28% higher apo B concentrations, 50% higher triglyceride concentrations, and 120% higher Lp(a) concentrations than FDB patients without clinical atherosclerosis. The haplotype background for the apo B-3500 mutation in these Danish families, as defined with seven markers, was comparable to that found in kindreds from the United States, Canada, Austria, Italy, and Germany. A polipoprotein B-100 (apo B-100) is the major struc-/ \ tural protein of low-density lipoproteins (LDLs) A. A . and very-low-density lipoproteins (VLDLs). Binding of apo B-100 to the LDL receptor is essential for the normal removal of LDL from plasma.1 A single G-to-A substitution in the codon for amino acid 3500 in the apo B protein causes a substitution of glutamine for arginine that reduces the binding affinity of apo B-100 for the LDL receptor.2 The clinical entity caused by this mutation, familial defective apo B-100 (FDB), is inherited as an autosomal dominant trait. The mutation has been found in many European populations and in immigrant populations of European descent. 3 The biochemical and clinical phenotype of the mutation is at present not entirely clear. 26 A thorough review of published and unpublished data from 135 FDB subjects from 56 families fied on the basis of a certain lipoprotein profile (ie, familial hypercholesterolemia or type Ila hyperlipidemia) or manifest atherosclerotic disease. As discussed by the authors, 7 the results are therefore likely to be biased by the selection method.Comparison of biochemical and clinical phenotypes in FDB subjects and non-FDB subjects from the same families, in which environmental and other genetic factor...

show abstract

“…This method allows incorporation of 40 figure legends for the exact LDL preparations used for each experiment). The animals were fasted 12 hours before the start of each experiment, fed 6 hours after the initial injection, and fed twice daily thereafter.…”

Section: Ldl Lysine Modifications To Block Ldl Receptor Bindingmentioning

confidence: 99%

Apolipoprotein B and a second major gene locus contribute to phenotypic variation of spontaneous hypercholesterolemia in pigs.

Aiello

Nevin

Ebert

et al. 1994

Arterioscler Thromb

View full text Add to dashboard Cite

The Lpb 5 apolipoprotein B (apoB) allele occurs in pigs with spontaneous hypercholesterolemia. Low-density lipoprotein (LDL) from these pigs binds to the LDL receptor with a lower affinity and is cleared from the circulation more slowly than control pig LDL. However, the severity of hypercholesterolemia in pigs with the mutant apoB allele is highly variable. This study aimed to determine the metabolic basis for the phenotypic heterogeneity among Lpb5 pigs. Lpb5 pigs were divided into two groups: those with plasma cholesterol greater than 180 mg/dL (Lpb5.1) and those with plasma cholesterol less than 180 mg/dL (Lpb5.2). LDL from both Lpb5.1 and Lpb5.2 pigs was catabolized in vivo and in vitro at a similarly reduced rate. The difference in plasma cholesterol between the two phenotypic groups was in part due to a higher buoyant LDL P opulation genetic studies have demonstrated that heredity contributes significantly to hyperlipidemia. In some instances, particular hyperlipidemic syndromes have been shown to be caused by single-gene mutations. However, the frequency of the known single-gene mutations is still far below the frequency of hyperlipidemia. The population studies therefore predict that multiple gene loci are involved and that in some instances there may be interactions between gene loci to produce a clinical syndrome.Apolipoprotein B (apoB) may be one such gene locus. ApoB is the primary protein component of low-density lipoprotein (LDL), which carries the bulk of cholesterol in human plasma, and is a ligand for the LDL receptor; thus, apoB functions in the assembly of the LDL particle and mediates its clearance from the blood. Given the central role of apoB in LDL metabolism, apoB mutations alone or in combination with other defects probably contribute significantly to hypercholesterolemia in the human population. One recently discovered apoB point mutation (Argjjoo->Gln) results in LDL particles with reduced LDL receptor binding activity and in some patients is associated with a reduced rate of LDL clearance from the plasma.1 This mutation is relatively common in the human population, Received July 19, 1993; revision accepted December 16, 1993. Hypercholesterolemia is also highly heritable in pigs. Rapacz et al 2 described a strain of pigs bearing an immunogenetically defined lipoprotein-associated marker, designated Lpb5, 3 and having marked hypercholesterolemia and premature atherosclerosis. The antiserum used to identify the Lpb5 pigs was shown to react only with apoB-100, 2 and the apoB gene from Lpb5 pigs has a unique 283-bp insertion at intron 28. 46In addition, Lpb5 pigs have LDL with defective binding to the LDL receptor 7 and delayed plasma clearance. 8These observations strongly suggest an association between apoB polymorphisms and hypercholesterolemia in pigs. However, pigs with the Lptr allele of apoB are phenotypically heterogeneous; the more severe phenotype (designated Lpb5.1) involves twofold to fourfold increases in plasma cholesterol, whereas a second phenotypic group (designa...

show abstract

Variation of Apolipoprotein-B Gene Is Associated With Obesity, High Blood Cholesterol Levels, and Increased Risk of Coronary Heart Disease

Cited by 111 publications

References 33 publications

Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study

Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study

Characteristics of 46 heterozygous carriers and 57 unaffected relatives in five Danish families with familial defective apolipoprotein B-100.

Apolipoprotein B and a second major gene locus contribute to phenotypic variation of spontaneous hypercholesterolemia in pigs.

Contact Info

Product

Resources

About