Lipoprotein concentrations in newborns are associated with allelic variations in their mothers

Descamps, Olivier; Bruniaux, Monique; Guilmot, P; Tonglet, René; Heller, F.

doi:10.1016/j.atherosclerosis.2003.11.002

Cited by 37 publications

(34 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are three reasons. Firstly, plasma cholesterol levels are lowest at birth [25] and increase rapidly in the first weeks of life, and then gradually until 2 years of age, when lipid levels become quite constant up to the adolescent growth spurt and are almost similar to those seen in young adults [26]. Secondly, dietary treatment is not recommended in the literature before the age of 2 years [26] (although one recent paper reported the safety of early dietary changes, as early as from 12 months onwards [27]).…”

Section: When To Screen?mentioning

confidence: 99%

Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization

et al. 2011

View full text Add to dashboard Cite

a b s t r a c tSince heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations.

show abstract

Section: When To Screen?mentioning

confidence: 99%

Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Maternal cholesterol in humans rises during pregnancy and cholesterol levels are affected by a number of factors, environmental and genetic. One candidate is therefore the APOE locus, either by its effects directly in the developing fetus, on fetal lipoprotein metabolism, or by affecting maternal cholesterol levels and materno-fetal lipoprotein metabolism [19,20]. A recent study has implicated maternal APOE variations as determinants of severity in SLOS [11].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the transfer of lipoproteins between the yolk sac and the developing fetus is critical in rodents, but apparently not so in humans. On the other hand, there is evidence in humans that fetal genotypes can affect maternal lipid levels [20]. This would suggest some biological crosstalk between these two entities.…”

Section: Discussionmentioning

confidence: 99%

“…It has been well established that the isoforms of APOE help determine the lipid and lipoprotein content of plasma; the ε4 allele is associated with higher and the ε2 allele with lower LDL-cholesterol and apolipoprotein B (APOB) levels [18] while higher plasma triglycerides are more commonly associated with the ε4 and ε2 alleles compared to ε3. Interestingly, the maternal APOE locus influences lipoprotein levels in newborns and vice versa; the ε2 isoform in newborns is associated with elevated maternal LDL-C and APOB levels and the same isoform in the mother is associated with a decreased in LDL-C and APOB and increased HDL-C levels in newborn cord blood [19,20]. Transfer of maternal cholesterol to embryos via the placenta and yolk sac has been documented in murine models [21].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse

Solcà

Pandit

et al. 2007

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

The Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic defect in cholesterol biosynthesis; mutations in the enzyme 3ß-hydroxysterol Δ7 reductase (Dhcr7) lead to a failure of cholesterol (and desmosterol) synthesis, with an accumulation of precursor sterols, such as 7-dehydrocholesterol. Extensive genotype-phenotype analyses have indicated that there is considerable variation in the severity of the disease, much of which is not explained by defects in the Dhcr7 gene alone. Factors ranging from variations in maternal-fetal cholesterol transfer during pregnancy, to other genetic factors have been proposed to account for this variability. Variations at the APOE locus affect plasma cholesterol levels in humans and this polymorphic gene has been found to be associated with cardiovascular as well as neurological disorders. This locus has recently been implicated in accounting for some of the variations in SLOS. To address whether maternal hypercholesterolemia can affect fetal outcome, we tested the ability of maternal hypercholesterolemia to rescue the neonatal lethality in a mouse model of SLOS. Maternal hypercholesterolemia, induced by ApoE or Ldl-r deficiency not only failed to ameliorate the postnatal lethality, it increased the prenatal mortality of Dhcr7 deficient pups. Thus the murine data suggest that maternal loss of ApoE or Ldl-r function further exacerbates the neonatal lethality, suggesting they may play a role in maternal transfer of cholesterol to the embryo.

show abstract

“…They were selected because single-nucleotide polymorphisms (SNPs) in these genes have been previously reported to affect lipid as well as lipoprotein levels (Table 1). 18,19,[23][24][25][26] Some common variants in the ABCA1 gene, such as the amino-acid exchange p.Arg1587Lys (R1587K), are known to result in low HDL cholesterol concentrations in the plasma, especially in women, as well as in higher plasma cholesterol and LDL levels. 20,21 Higher risk for ischemic heart disease and coronary heart disease was postulated in persons carrying the KK genotype (homozygous for p.Lys1587).…”

Section: Introductionmentioning

confidence: 99%

Maternal ABCA1 genotype is associated with severity of Smith–Lemli–Opitz syndrome and with viability of patients homozygous for null mutations

et al. 2012

View full text Add to dashboard Cite

The Smith-Lemli-Opitz syndrome (SLOS [MIM 270400]) is an autosomal recessive malformation syndrome that shows a great variability with regard to severity. SLOS is caused by mutations in the D7sterol-reductase gene (DHCR7), which disrupt cholesterol biosynthesis. Phenotypic variability of the disease is already known to be associated with maternal apolipoprotein E (ApoE) genotype. The aim of this study was to detect additional modifiers of the SLOS phenotype. We examined the association of SLOS severity with variants in the genes for ApoC-III, lecithin-cholesterol acyltransferase, cholesteryl-ester transfer protein, ATP-binding cassette transporter A1 (ABCA1), and methylene tetrahydrofolate reductase. Our study group included 59 SLOS patients, their mothers, and 49 of their fathers. In addition, we investigated whether ApoE and ABCA1 genotypes are associated with the viability of severe SLOS cases (n ¼ 21) caused by two null mutations in the DHCR7 gene. Maternal ABCA1 genotypes show a highly significant correlation with clinical severity in SLOS patients (P ¼ 0.007). The rare maternal p.1587Lys allele in the ABCA1 gene was associated with milder phenotypes. ANOVA analysis demonstrated an association of maternal ABCA1 genotypes with severity scores (logarithmised) of SLOS patients of P ¼ 0.004. Maternal ABCA1 explains 15.4% (R 2 ) of severity of SLOS patients. There was no association between maternal ApoE genotype and survival of the SLOS fetus carrying two null mutations. Regarding ABCA1 p.Arg1587Lys in mothers of latter SLOS cases, a significant deviation from HardyWeinberg equilibrium (HWE) was observed (P ¼ 0.005). ABCA1 is an additional genetic modifier in SLOS. Modifying placental cholesterol transfer pathways may be an approach for prenatal therapy of SLOS.

show abstract

Lipoprotein concentrations in newborns are associated with allelic variations in their mothers

Cited by 37 publications

References 37 publications

Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization

Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization

Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse

Maternal ABCA1 genotype is associated with severity of Smith–Lemli–Opitz syndrome and with viability of patients homozygous for null mutations

Contact Info

Product

Resources

About