Association of the apolipoprotein E4 allele with hypercholesterolemia in apparently healthy male adults in Tokyo

Tsuchiya, Shigeru; Yamanouchi, Yasuko; Miyazaki, Ryunosuke; Yanagi, Hisako; Yamakawa, Katsutoshi; Yuzawa, Kenji; Ohnuki, Masahiro; Hamaguchi, Hideo

doi:10.1007/bf01910283

Cited by 7 publications

(4 citation statements)

References 20 publications

(13 reference statements)

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“…Nine apoE variants (p.Glu21Lys, p.Leu46Pro, p.Gln99Lys-E4, p. Pro102Arg, p.Arg163Cys, p.Leu167del, apoE7-Suita, p.Arg269Gly, p. Leu270Glu) have been observed in single cases with hyperLDLemia (type IIa hyperlipoproteinemia), but the possible co-segregation with hypercholesterolemia in the families was not always analyzed [24,27,[46][47][48][52][53][54][55][56][57][58] (Table 1).…”

Section: Apoe and Autosomal Dominant Hypercholesterolemia (Adh)mentioning

confidence: 99%

APOE gene variants in primary dyslipidemia

et al. 2021

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Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations in lipid and lipoprotein levels and thus cardiovascular risk. The isoform apoE4 is associated with an increase in LDL-cholesterol levels and thus a higher cardiovascular risk compared to apoE3. Whereas, apoE2 is associated with a mild decrease in LDL-cholesterol levels. In the presence of other risk factors, apoE2 homozygotes could develop type III hyperlipoproteinemia (familial dysbetalipoproteinemia or FD), an atherogenic disorder characterized by an accumulation of remnants of triglyceride-rich lipoproteins. Several rare APOE gene variants were reported in different types of dyslipidemias including FD, familial combined hyperlipidemia (FCH), lipoprotein glomerulopathy and bona fide autosomal dominant hypercholesterolemia (ADH). ADH is characterized by elevated LDL-cholesterol levels leading to coronary heart disease, and due to molecular alterations in three main genes: LDLR, APOB and PCSK9. The identification of the APOE-p.Leu167del variant as the causative molecular element in two different ADH families, paved the way to considering APOE as a candidate gene for ADH. Due to non mendelian interacting factors, common genetic and environmental factors and perhaps epigenetics, clinical presentation of lipid disorders associated with APOE variants often strongly overlap. More studies are needed to determine the spectrum of APOE implication in each of the diseases, notably ADH, in order to improve clinical and genetic diagnosis, prognosis and patient management. The purpose of this review is to comment on these APOE variants and on the molecular and clinical overlaps between dyslipidemias.

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Section: Apoe and Autosomal Dominant Hypercholesterolemia (Adh)mentioning

confidence: 99%

APOE gene variants in primary dyslipidemia

et al. 2021

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“…Several studies on the association of APOE4 with hypercholesterolemia in adults have been performed (Utermann et al 1984, Leren et al 1985, Tsuchiya et al 1987. Little work, however, has been dedicated to studying the effects of APOE phenotype on lipid metabolism in children.…”

Section: Discussionmentioning

confidence: 99%

“…APOE3 and APOE4, respectively (Zannis et al 1981, Utermann et al 1982. Several reports have shown the association of hypercholesterolemia and APOE4 in adults (Utermann et al 1984, Leren et al 1985, Tsuchiya et al 1987). However, the association of the APOE4 phenotype and hypercholesterolemia in children has yet to be demonstrated.…”

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confidence: 99%

Association of hypercholesterolemia and apolipoprotein E4 in school children

Yanagi¹,

Shimakura

Yamanouchi³

et al. 1990

Clinical Genetics

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To investigate the association of apolipoprotein (APO) E4 and hypercholesterolemia in children, we studied the APOE phenotypes of 51 school‐age children with hypercholesterolemia and of 51 age, sex and obesity index‐matched controls with normocholesterolemia by two‐dimensional gel electrophoresis. APOE4 was present in 21 of 51 hypercholesterolemic children (41.2%), and in nine of 51 control subjects (17.6%). The difference was significant (p<0.01). This finding indicates that APOE4 is associated with hypercholesterolemia in children.

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“…These variants have also been found in several unrelated patients with atherosclerotic disease (Yamamura et al 1984b). Apo E5 (Glu3+Lys) and E7 (Glu244+Lys, Glu245+Lys) have been found only in Japanese subjects (Tajima et al 1989, Maeda et al 1989a, Maeda et al 1989b, Kitahara et al 1990, Tsuchiya et al 1987, Yanagi et al 1990).…”

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confidence: 93%

Population frequency of apolipoprotein E5 (Glu3→Lys) and E7 (Glu244→Lys, Glu245→Lys) variants in western Japana

et al. 1995

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Apolipoprotein (apo) E modulates the catabolism of chylomicrons and of very low density lipoprotein remnants. It has three major isoforms (apo E2, E3, E4) and some rare variants. To detect the variants of apo E, blood specimens from 1269 Japanese subjects were analyzed using isoelectric focusing with immunoblotting. The E5 and E7 variants were identified by IEF in 2 and 18 subjects, respectively. Both E5 (Glu3→Lys) carriers were confirmed by PCR‐mediated site‐directed mutagenesis, and all E7 (Glu244→Lys, Glu245→Lys) carriers were confirmed by the amplification refractory mutation system. The relative frequencies of the ε5 and ε7 alleles were 0.001 and 0.007, respectively. High concentrations of total cholesterol (>220 mg/dl) were detected in five of the subjects expressing apo E7 and one subject expressing apo E5, and eight subjects heterozygous for apo E7 showed elevated plasma triglyceride concentrations (>150 mg/dl). In 621 healthy subjects, the mean triglyceride concentration in subjects with apo E7/3 appeared to be higher than in those with apo E3/3, but the difference was not statistically significant.

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Association of the apolipoprotein E4 allele with hypercholesterolemia in apparently healthy male adults in Tokyo

Cited by 7 publications

References 20 publications

APOE gene variants in primary dyslipidemia

APOE gene variants in primary dyslipidemia

Association of hypercholesterolemia and apolipoprotein E4 in school children

Population frequency of apolipoprotein E5 (Glu3→Lys) and E7 (Glu244→Lys, Glu245→Lys) variants in western Japana

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