Genetic variation in the apolipoprotein AI-CIII-AIV gene cluster and coronary heart disease

Paulweber, Bernhard; Friedl, Walter; Krempler, Franz; Humphrie, Steve; Sandhofer, F

doi:10.1016/0021-9150(88)90033-0

Cited by 59 publications

(27 citation statements)

References 22 publications

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“…Our results concerning plasma lipids are consistent with findings reported by other investigators [8, 9, 16±18]. The authors of these studies reported that in heterozygous carriers of the Gly188Glu or Pro207Leu mutation expression of hypertriglyceridaemia is dependent on age, obesity and diabetes [8,9,22]. In our study, carriers had significantly higher levels of plasma triglycerides, even after adjustment for age, sex and BMI.…”

Section: Discussionsupporting

confidence: 93%

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Hölzl¹,

Iglseder

Sandhofer

et al. 2002

Diabetologia

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Section: Discussionsupporting

confidence: 93%

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Hölzl¹,

Iglseder

Sandhofer

et al. 2002

Diabetologia

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“…The degree of linkage disequilibrium between the two RFLPs was estimated by using the correlation coefficient A. 28 Since no chromosome of the haplotype X2R2 was observed unambiguously, the haplotypes of individuals doubly heterozygous for the two RFLPs were all assumed to be X1R2 and X2R1. A result was considered to be statistically significant at/O<0.05.…”

Section: Discussionmentioning

confidence: 99%

Association of DNA polymorphism at the apolipoprotein B gene locus with coronary heart disease and serum very low density lipoprotein levels.

et al. 1990

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The role of genetic variation at the 3' end of the apolipoprotein B gene locus In the development of coronary heart disease and the regulation of the serum levels of various lipoprotelns was studied by using two common restriction fragment length polymorphisms detected with the enzymes Xba I and EcoR I. A group of 106 male patients with coronary heart disease and 118 matched controls of Austrian origin were Investigated. The frequency of the R2 allele of the EcoR I polymorphism at cDNA position 12 669 defined by the absence of the polymorphic EcoR I cutting site was significantly higher among patients than among controls. The controls with the R2 allele had significantly higher levels of total triglycerides, very low density lipoprotein (VLDL) triglycerides, and VLDL cholesterol than did the controls without this allele. Among the patients, the R2 allele was associated with higher serum VLDL apolipoprotein B levels. The chemical composition of VLDL In Individuals with different genotypes for the EcoR I polymorphism did not differ significantly. For the Xba I polymorphism at cDNA position 7673, no correlation with coronary risk could be demonstrated. Patients and controls homozygous for the X2 allele characterized by the presence of the polymorphic Xba I cutting site showed a higher total and low density lipoprotein cholesterol level than did subjects with the genotype X1X1 or X1X2. This difference, however, was not statistically significant. These findings Indicate that the R2 allele of the EcoR I polymorphism Is associated with the occurrence of coronary heart disease and that variation at the 3' end of the apo B gene Is Involved In the regulation of VLDL metabolism.

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“…2021 The predominance of small, dense LDL as determined by gradient gel electrophoresis, denoted LDL subclass phenotype B, has been associated with increased apoB levels. 24 ApoB levels also vary with polymorphisms at the apoA-I/C-III/A-IV gene cluster, 29 the apoE structural locus, 30 and possibly the apoB structural locus, 31 -32 although the apoB and apoE polymorphisms have not been specifically associated with FCHL. 33 If elevated apoB levels are involved in the etiology of FCHL, this may be one source of the etiologic heterogeneity in this disorder.…”

Section: F Amilial Combined Hyperlipidemia (Fchl) Ismentioning

confidence: 99%

Genetic predictors of FCHL in four large pedigrees. Influence of ApoB level major locus predicted genotype and LDL subclass phenotype.

Jarvik

Brunzell

Austin

et al. 1994

Arterioscler Thromb

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The genetic basis of familial combined hyperlipidemia (FCHL) has eluded investigators for 20 years, despite the apparent segregation of FCHL as an autosomal dominant disorder affecting 1% to 2% of individuals. Etiologic heterogeneity and additive effects of traits controlled by other genetic loci have been suggested. Two traits have been implicated in FCHL. The first is the predominance of a small, dense low-density lipoprotein (LDL), LDL subclass phenotype B, which segregates as a mendelian trait. The second is a mendelian locus with large effects on apolipoprotein (apo) B levels that is defined by complex segregation analysis (predicted apoB level genotype). This study shows that these factors F amilial combined hyperlipidemia (FCHL) is characterized by variable expression of hypercholesterolemia and hypertriglyceridemia in a given family, with either or both present in affected individuals.1 FCHL is associated with an excess risk of coronary artery disease (CAD) and was first reported by Goldstein et al 1 in 1973 in pedigrees ascertained through men who were survivors of myocardial infarction; over 10% of those probands were considered to have FCHL. One half to one third of familial premature CAD 2 and at least 10% of all premature CAD 1 -3 are ascribed to FCHL. This disorder is estimated to affect 1% to 2% of those in the populations studied and may be responsible for 5% of myocardial infarctions.1 While the inheritance of FCHL was originally described as consistent with an autosomal dominant disorder with full penetrance by the end of the third decade, 1 formal segregation analysis, adjusting for ascertainment, has not been reported. 4 Thus, the mode of inheritance remains uncertain.Efforts to refine the phenotype of FCHL have led to the observation that elevated levels of apolipoprotein Received May 4, 1994; revision accepted July 19, 1994. O 1994 American Heart Association, Inc.appear to be separate genetic effects, both of which aid in the prediction of FCHL in four large pedigrees. The results suggest that FCHL may be best predicted by a threshold model in which apoB level genotype and LDL subclass phenotype each act to increase the risk of FCHL. Heterogeneity in the transmission of apoB levels among families is suggested, supporting the etiologic heterogeneity of FCHL. These results emphasize the advantages inherent in the study of large pedigrees when disease heterogeneity is suspected.

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Genetic variation in the apolipoprotein AI-CIII-AIV gene cluster and coronary heart disease

Cited by 59 publications

References 22 publications

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Association of DNA polymorphism at the apolipoprotein B gene locus with coronary heart disease and serum very low density lipoprotein levels.

Genetic predictors of FCHL in four large pedigrees. Influence of ApoB level major locus predicted genotype and LDL subclass phenotype.

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