A novel apolipoprotein E5 variant with a 24-bp insertion causing hyperlipidemia

Yamanouchi, Yasuko; Takano, Toshiya; Hamaguchi, Hideo; Tokunaga, Katsushi

doi:10.1007/s100380170014

Cited by 6 publications

(2 citation statements)

References 25 publications

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“…Of the above-mentioned 50 tandem duplications associated with flanking direct repeats (for which inserted sequences were identifiable), only 15 were discussed in terms of their underlying mutational mechanisms in the original publications and only five were proposed to result from replication slippage [Kornreich et al, 1990;Bashir et al, 1998;Hughes et al, 2000;Vervoort et al, 2000;Yamanouchi et al, 2001]; the remaining 10 were thought to be generated by unequal crossing over [Tiller et al, 1990;Stoppa-Lyonnet et al, 1991;Oshima et al, 1992;Marcus et al, 1993;Wildin et al, 1994;Hamalainen et al, 1996;Bianchi et al, 1997;Puget et al, 1999;Smith and Sperling, 1999;Kawakami et al, 2002]. However, of the 50 tandem duplications, 47 are associated with short direct repeats of 2-11 bp; the remaining three are associated with longer direct repeats of 18 bp (the 1,857-bp duplication in Marcus et al [1993]), 39 bp (the 3,180-bp duplication in Stoppa-Lyonnet et al [1991]), and 49 bp (the 6,081-bp duplication in Puget et al [1999]), respectively (see Supplementary Table S2).…”

Section: Normal Replicationmentioning

confidence: 99%

Meta‐Analysis of gross insertions causing human genetic disease: Novel mutational mechanisms and the role of replication slippage

et al. 2005

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Although gross insertions (>20 bp) comprise <1% of disease-causing mutations, they nevertheless represent an important category of pathological lesion. In an attempt to study these insertions in a systematic way, 158 gross insertions ranging in size between 21 bp and approximately 10 kb were identified using the Human Gene Mutation Database (www.hgmd.org). A careful meta-analytical study revealed extensive diversity in terms of the nature of the inserted DNA sequence and has provided new insights into the underlying mutational mechanisms. Some 70% of gross insertions were found to represent sequence duplications of different types (tandem, partial tandem, or complex). Although most of the tandem duplications were explicable by simple replication slippage, the three complex duplications appear to result from multiple slippage events. Some 11% of gross insertions were attributable to nonpolyglutamine repeat expansions (including octapeptide repeat expansions in the prion protein gene [PRNP] and polyalanine tract expansions) and evidence is presented to support the contention that these mutations are also caused by replication slippage rather than by unequal crossing over. Some 17% of gross insertions, all >or=276 bp in length, were found to be due to LINE-1 (L1) retrotransposition involving different types of element (L1 trans-driven Alu, L1 direct, and L1 trans-driven SVA). A second example of pathological mitochondrial-nuclear sequence transfer was identified in the USH1C gene but appears to arise via a novel mechanism, trans-replication slippage. Finally, evidence for another novel mechanism of human genetic disease, involving the possible capture of DNA oligonucleotides, is presented in the context of a 26-bp insertion into the ERCC6 gene.

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Section: Normal Replicationmentioning

confidence: 99%

Meta‐Analysis of gross insertions causing human genetic disease: Novel mutational mechanisms and the role of replication slippage

et al. 2005

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“…In particular, a marked difference in the LDL-cholesterol level was observed, which agrees with the results reported for European and American populations. 5,6,21) Apo E genotypes were determined by a highly accurate DNA analysis using the PCR-SSCP method, 18) by which the base sequence of the entire apo E-coding region and genotypes were determined, to avoid confusion caused by multiple variant genotypes. After adjustment for age and BMI, it was found that the apo E genotype significantly affected LDL-cholesterol (p < 0.001) and serum total cholesterol (p < 0.01) levels.…”

Section: Discussionmentioning

confidence: 99%

Effect of Apolipoprotein E Genotype on Association of Menopausal Status with Lipid Level in Japanese Women

Yamanouchi

Hashimoto

Yamaoka

et al. 2006

JOURNAL OF HEALTH SCIENCE

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Serum lipid level increases during hormonal transition before and after menopause. In Caucasians, changes in lipid level after menopause across apolipoprotein E (apo E) genotypes were studied. We investigated 159 Japanese healthy female workers (age range, 35-63). The apo E genotypes were determined by the polymerase chain reaction single-strand conformation polymorphisms method for the entire apo E-coding region. The low-density lipoprotein cholesterol (LDL-cholesterol) level significantly varied according to the apo E genotype, but not according to the menopausal status after adjusting for age and body mass index (p < 0.001). The effect of menopause on LDLcholesterol level significantly varied depending on the apo E genotype (p < 0.05). Apo E2 [APOE, R158C] carriers in the senium period had a lower LDL-cholesterol level than those in the fertile period (81.5 ± 12.0 mg/dl vs. 122.3 ± 12.9 mg/dl). In contrast, apo E3 homozygotes in the senium period showed a higher LDL-cholesterol level than those in the fertile period (140.9 ± 7.0 mg/dl vs. 134.1 ± 6.1 mg/dl). The LDL-cholesterol levels of apo E4 [APOE, C112R] carriers were the similar for the two periods. These results indicate that the serum lipid control in perimenopausal women should be customized according to the apo E genotype for the promotion of women's health in Japan.Key words ---menopause, lipid levels, apolipoprotein E genotype, polymerase chain reaction-single strandard conformation polymorphism, Japanese women, low-density lipoprotein cholesterol caused by changes in blood lipid levels after sexhormone transition.1-4) It was reported that menopause causes increases in the levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), triglyceride and apolipoprotein B, as well as decreases in the levels of high-density lipoprotein cholesterol (HDL-cholesterol) and apolipoprotein AI.5-6) A recent survey in Japan, where the diet and lifestyles are different from those in North America, has also showed that the serum total cholesterol level (< 220 mg/dl) in 50.9% of women in their fifties exceeded the recommended level.7) However, the data were derived from a crosssectional survey, and the results may be confounded by age and factors other than menopause. Indeed, some women are normolipidemic even after menopause, which is not fully explained by the menopausal status and lifestyles. Genetic property would be another factor, but this is a poorly examined issue in studies of women and serum lipid levels.

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Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup)

Yokochi,

Matsunaga,

Kanemoto

et al. 2024

CEN Case Rep

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A novel apolipoprotein E5 variant with a 24-bp insertion causing hyperlipidemia

Cited by 6 publications

References 25 publications

Meta‐Analysis of gross insertions causing human genetic disease: Novel mutational mechanisms and the role of replication slippage

Meta‐Analysis of gross insertions causing human genetic disease: Novel mutational mechanisms and the role of replication slippage

Effect of Apolipoprotein E Genotype on Association of Menopausal Status with Lipid Level in Japanese Women

Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup)

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