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• W1982393747 abstract "To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (−21 ± 9 mg/dl), lower LDL-cholesterol (LDL-C; −12 ± 5 mg/dl), lower apoB (−14 ± 4 mg/dl), higher HDL-C (5 ± 2 mg/dl), and higher apoA-I (9 ± 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 ± 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 ± 6 mg/dl) and higher maternal apoB (14 ± 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids.Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease). To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (−21 ± 9 mg/dl), lower LDL-cholesterol (LDL-C; −12 ± 5 mg/dl), lower apoB (−14 ± 4 mg/dl), higher HDL-C (5 ± 2 mg/dl), and higher apoA-I (9 ± 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 ± 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 ± 6 mg/dl) and higher maternal apoB (14 ± 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids. Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease). Whether human placenta plays an important role in the metabolism of lipoproteins in the pregnant woman still remains unclear (1Woolet L.A. The origins and roles of cholesterol and fatty acids in the fetus.Curr. Opin. Lipidol. 2000; 12: 305-312Crossref Scopus (70) Google Scholar). Although this idea is consistent with the assumption that maternal lipoproteins supply lipids to the fetus via the placenta, at present it is only supported by in vitro arguments: immunochemistry and RNA hybridization in placental tissues demonstrated the presence of some key players of lipoprotein metabolism (lipoprotein lipases, receptors, and apolipoproteins) (2Huter O. Wolf H.J. Schnetzer A. Pfaller K. Lipoprotein lipase, LDL receptor and apolipoprotein in human fetal membrane at term.Placenta. 1997; 18: 707-715Crossref PubMed Scopus (12) Google Scholar, 3Waterman I.J. Emmison N. Dutta-Roy A.K. Characterization of triacylglycerol hydrolase activities in human placenta.Biochim. Biophys. Acta. 1998; 1394: 169-176Crossref PubMed Scopus (45) Google Scholar, 4Furuhashi M. Seo H. Mizutani S. Narita O. Tomoda Y. Matsui N. Expression of low density lipoprotein receptor gene in human placenta during pregnancy.Mol. Endocrinol. 1989; 3: 1252-1256Crossref PubMed Scopus (48) Google Scholar, 5Jaye M. Lynch K.J. Krawiec J. Marchadier D. Maugeais C. Doan K. South V. Amin D. Perrone M. Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism.Nat. Genet. 1999; 21: 424-428Crossref PubMed Scopus (418) Google Scholar, 6Wittmaack F.M. Gafvels M.E. Bronner M. Matsuo H. McCrae K.R. Tomaszewski J.E. Robinson S.L. Strickland D.K. Strauss III. J.F. Localization and regulation of the human very low density lipoprotein/apolipoprotein E receptor: trophoblast expression predicts a role for the receptor in the placental lipid transport.Endocrinology. 1995; 136: 340-348Crossref PubMed Scopus (0) Google Scholar, 7Fischer U. Birkenmeier G. Horn L.C. Localization of alpha(2)-macroglobulin receptor/low-density lipoprotein receptor in third-trimester human placentas: a preliminary immunohistochemical study.Gynecol. Obstet. Invest. 2001; 52: 22-25Crossref PubMed Scopus (7) Google Scholar, 8Bonet B. Brunzell J.D. Gown A.M. Knopp R.H. Metabolism of very-low density lipoprotein triglycerides by human placental cells: the role of lipoprotein lipase.Metabolism. 1992; 41: 596-603Abstract Full Text PDF PubMed Scopus (79) Google Scholar, 9Nilsson-Ehle P. Garfinkel A.S. Schotz M.C. Lipolytic enzymes and plasma lipoprotein metabolism.Annu. Rev. Biochem. 1980; 49: 667-693Crossref PubMed Scopus (571) Google Scholar), whereas tissue cultures of placental fragments indicated the capture and hydrolysis (10Grimes R.W. Pepe G.J. Albrecht E.D. Regulation of human placental trophoblast low-density lipoprotein uptake in vivo by estrogen.J. Clin. Endocrinol. Metab. 1996; 81: 2675-2679PubMed Google Scholar, 11Rindler M.J. Traber M.G. Esterman A.L. Berseinger N.A. Dancis J. Synthesis and secretion of apolipoprotein E by human placenta and choriocarcinoma cell lines.Placenta. 1991; 12: 615-624Crossref PubMed Scopus (44) Google Scholar, 12Mallov S. Alousi A.A. Lipoprotein lipase activity of rat and human placenta.Proc. Soc. Exp. Biol. Med. 1965; 119: 301-306Crossref PubMed Scopus (24) Google Scholar, 13Rothwell J.E. Elphick M.C. Lipoprotein lipase activity in human and guinea-pig placenta.J. Dev. Physiol. 1982; 4: 153-159PubMed Google Scholar) as well as the synthesis and secretion (14Madsen E.M. Lindegaard M.L.S. Andersen C.B. Damm P. Nielsen L.B. Human placenta secretes apolipoprotein B-100 containing lipoproteins.J. Biol. Chem. 2004; 279: 55271-55276Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar) of lipoproteins. However, in vivo evidence is still lacking in humans. Furthermore, the simple idea of a substantial lipid transfer between mother and fetus remains challenged by the absence of a strong correlation between the concentrations of lipoproteins in pregnant women and in their newborns at birth [see (15Descamps O.S. Bruniaux M. Guilmot P.F. Tonglet R. Heller F.R. Lipoprotein concentrations in newborns are associated with allelic variations in their mothers.Atherosclerosis. 2004; 172: 287-298Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar) for references]. To explore the hypothesis that placental proteins contribute effectively to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded by genes belonging to the fetal genome. Under these conditions, the demonstration of an association between genetic polymorphisms present in newborns and variations of lipoprotein concentrations in their mothers may argue in favor of the hypothesis. For several reasons, we focused our attention on the common polymorphisms of the genes of lipoprotein lipase [LPL*S447X and LPL*N291S (16Hokanson J.E. Functional variants in the lipoprotein lipase gene and risk of cardiovascular disease.Curr. Opin. Lipidol. 1999; 10: 393-399Crossref PubMed Scopus (76) Google Scholar)], apolipoprotein E [APOE*E2 and APOE*E4 (17Eichner J.E. Dunn S.T. Perveen G. Thompson D.M. Stewart K.E. Stroehla B.C. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review.Am. J. Epidemiol. 2002; 155: 487-519Crossref PubMed Scopus (616) Google Scholar)], and apolipoprotein C-III [APOC3*S2 (18Shachter N.S. Apolipoprotein C-I and C-III as important modulators of lipoprotein metabolism.Curr. Opin. Lipidol. 2001; 12: 297-304Crossref PubMed Scopus (248) Google Scholar)]. First, these genes are known to be involved in the metabolism of triglyceride-rich lipoproteins, which dramatically increase in concentration during pregnancy (19Fahreaus L. Larsson-Cohn U. Wallentin L. Plasma lipoproteins including high density lipoprotein subfractions during normal pregnancy.Obstet. Gynecol. 1985; 66: 468-477PubMed Google Scholar). Second, two of these genes, LPL and APOE, are abundantly expressed in the placenta (2Huter O. Wolf H.J. Schnetzer A. Pfaller K. Lipoprotein lipase, LDL receptor and apolipoprotein in human fetal membrane at term.Placenta. 1997; 18: 707-715Crossref PubMed Scopus (12) Google Scholar, 3Waterman I.J. Emmison N. Dutta-Roy A.K. Characterization of triacylglycerol hydrolase activities in human placenta.Biochim. Biophys. Acta. 1998; 1394: 169-176Crossref PubMed Scopus (45) Google Scholar, 11Rindler M.J. Traber M.G. Esterman A.L. Berseinger N.A. Dancis J. Synthesis and secretion of apolipoprotein E by human placenta and choriocarcinoma cell lines.Placenta. 1991; 12: 615-624Crossref PubMed Scopus (44) Google Scholar), whereas APOC3 is less expressed in placenta and in fetus (20Zannis V.I. Cole F.C. Jackson C.L. Kurnit D.M. Karathanassis S.K. Distribution of apolipoprotein A-I, C-II, C-III and E mRNA in fetal human tissues. Time-dependent induction of apolipoprotein E mRNA by cultures of human monocyte-macrophages.Biochemistry. 1985; 24: 4450-4455Crossref PubMed Scopus (147) Google Scholar), offering the possibility to compare the influence of genes variably expressed by the placenta. Third, their polymorphisms are well known for their associations with lipoprotein concentrations in adults (16Hokanson J.E. Functional variants in the lipoprotein lipase gene and risk of cardiovascular disease.Curr. Opin. Lipidol. 1999; 10: 393-399Crossref PubMed Scopus (76) Google Scholar, 17Eichner J.E. Dunn S.T. Perveen G. Thompson D.M. Stewart K.E. Stroehla B.C. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review.Am. J. Epidemiol. 2002; 155: 487-519Crossref PubMed Scopus (616) Google Scholar, 18Shachter N.S. Apolipoprotein C-I and C-III as important modulators of lipoprotein metabolism.Curr. Opin. Lipidol. 2001; 12: 297-304Crossref PubMed Scopus (248) Google Scholar), and the mechanisms by which these associations occur have been linked directly to quantitative or qualitative alterations of the proteins encoded by these genes. In adults, the S447X allele of LPL, which enhances the lipolytic activity of the enzyme, is associated with lower triglycerides and higher HDL-cholesterol (HDL-C), whereas the N291S allele of LPL, which reduces the activity of the enzyme, is associated with increased triglycerides and reduced HDL-C (16Hokanson J.E. Functional variants in the lipoprotein lipase gene and risk of cardiovascular disease.Curr. Opin. Lipidol. 1999; 10: 393-399Crossref PubMed Scopus (76) Google Scholar). The S2 allele of APOC3 is also associated with higher triglycerides in adults, because of the hepatic overproduction of apolipoprotein C-III, an inhibitor of lipoprotein lipase (18Shachter N.S. Apolipoprotein C-I and C-III as important modulators of lipoprotein metabolism.Curr. Opin. Lipidol. 2001; 12: 297-304Crossref PubMed Scopus (248) Google Scholar). The E2 allele of APOE is associated with lower LDL-C, because of the lower affinity of the isoform apoE2 for the apoE receptor (→ delayed clearance of apoE-rich chylomicron remnants → depletion of hepatocyte pool of cholesterol → overexpression of LDL receptor → increased clearance of LDL particles) (17Eichner J.E. Dunn S.T. Perveen G. Thompson D.M. Stewart K.E. Stroehla B.C. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review.Am. J. Epidemiol. 2002; 155: 487-519Crossref PubMed Scopus (616) Google Scholar, 21Weisgraber K.H. Innerarity T.L. Mahley R.W. Abnormal lipoprotein receptor binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site.J. Biol. Chem. 1982; 257: 2518-2521Abstract Full Text PDF PubMed Google Scholar). Finally, a previous study in pregnant women has shown that polymorphisms (APOE*E2, LPL*S447X, and LPL*N291S) present in the genome of these women were associated with variations of their own lipoprotein concentrations (22McGladdery S.H. Frohlich J.J. Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy.J. Lipid Res. 2001; 42: 1905-1912Abstract Full Text Full Text PDF PubMed Google Scholar). Here, we describe, for the first time, associations between genetic polymorphisms carried by newborns and variations of lipoprotein concentrations in their mothers. The present study was part of a project (15Descamps O.S. Bruniaux M. Guilmot P.F. Tonglet R. Heller F.R. Lipoprotein concentrations in newborns are associated with allelic variations in their mothers.Atherosclerosis. 2004; 172: 287-298Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar) aimed at characterizing the reciprocal influences between the lipoprotein metabolisms of pregnant women and of their children at the end of gestation. As described previously (15Descamps O.S. Bruniaux M. Guilmot P.F. Tonglet R. Heller F.R. Lipoprotein concentrations in newborns are associated with allelic variations in their mothers.Atherosclerosis. 2004; 172: 287-298Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar), 525 mothers and their newborns were consecutively recruited in the maternity ward of our hospital based on the following criteria: Caucasian origin, eutocic delivery with cephalic presentation after a programmed labor induction (to allow the standardization of blood sampling) between the beginning of the 37th week and the end of the 41st week, singleton live birth, no gestational complication, no diabetes, no congenital malformation or perinatal problem, body weight between 2,500 and 3,999 g, Apgar score of ⩾7 during the first minute and ⩾9 by the 5th minute. All mothers gave informed consent, and the ethical committee of the hospital approved the study protocol. We analyzed the concentrations of cholesterol, triglycerides, HDL-C, LDL-C, apoB, and apoA-I (referred in the text as the “maternal lipids” and “newborn lipids”) in the peripheral blood of mothers taken at the start of the labor induction and in the cord of newborns at birth. We also recorded “maternal nonlipid factors,” such as age, smoking status, weight and height of the mothers before delivery, and “newborn nonlipid factors,” such as sex, gestational age, weight, height, body mass index, head circumference, and Apgar score of the newborns. Because the women were recruited upon entering the delivery room in the obstetrical unit and their weight before pregnancy was recorded in only 142 (27%) obstetrical files, we collected these data retrospectively in 279 (53%) other women, whereas they remained unknown for 104 women (19%). The weight gain during pregnancy was calculated in these 142 and 279 women. Newborn and maternal DNA were analyzed for the following polymorphisms: the C-to-G transversion at nucleotide 1,595 in exon 9 of the LPL gene, converting serine to a premature termination (the LPL*S447X allele) (16Hokanson J.E. Functional variants in the lipoprotein lipase gene and risk of cardiovascular disease.Curr. Opin. Lipidol. 1999; 10: 393-399Crossref PubMed Scopus (76) Google Scholar); the A-to-G transition at nucleotide 1,127 in exon 6 of the LPL gene, converting asparagine to serine (the LPL*N291S allele) (16Hokanson J.E. Functional variants in the lipoprotein lipase gene and risk of cardiovascular disease.Curr. Opin. Lipidol. 1999; 10: 393-399Crossref PubMed Scopus (76) Google Scholar); the variants E2 and E4 (the APOE*E2 or APOE*E4 allele) of the APOE gene (17Eichner J.E. Dunn S.T. Perveen G. Thompson D.M. Stewart K.E. Stroehla B.C. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review.Am. J. Epidemiol. 2002; 155: 487-519Crossref PubMed Scopus (616) Google Scholar); and the G-to-C transversion at nucleotide 3,238 in the 3′ untranslated region (called APOC3*S2 because it is detectable by SstI restriction fragment-length polymorphism; the wild type is S1) of the APOC3 gene (18Shachter N.S. Apolipoprotein C-I and C-III as important modulators of lipoprotein metabolism.Curr. Opin. Lipidol. 2001; 12: 297-304Crossref PubMed Scopus (248) Google Scholar). Because of the very low frequencies of homozygous genotypes for the less common alleles of these polymorphisms, we defined dichotomically the “genetic factor” as “carriage” and “noncarriage” of the less common allele(s) rather than on the basis of the genotypes: LPL*S447X+ (Ser/Stop or Stop/Stop at codon 447) and LPL*S447X− (Ser/Ser at codon 447); LPL*N291S+ (Asn/Ser or Ser/Ser at codon 291) and LPL*N291S− (Asn/Asn at codon 291); APOC3*S+ (S2/S2 or S1/S2) and APOC3*S2− (S1/S1); APOE*E2+ (E2/E2 or E3/E2), APOE*E4+ (E4/E3 or E4/E4), and APOE*E3E3 (E3/E3). Because alleles E2 and E4 are known to determine opposite biological effects, we excluded the E2+ mothers with an E4+ newborn and E4+ mothers with an E2+ newborn. Our hypothesis was that lipids of pregnant women are associated with the genetic factors of their newborns, independently of their own genetic factors. Our strategy consisted primarily of comparing, two by two, lipids of different groups of mothers classified according to their genetic status and the genetic status of their newborns (seven groups for the APOE gene and four for the other loci). After having collected the first 100 mothers, we estimated the sample size from the data on the two major blood lipids (LDL-C ∼ 165 ± 45 mg/dl and triglyceride ∼ 260 ± 70 mg/dl): to detect a 15% difference between two groups requires at least 52 mothers in each group for a two-sided significance level of 0.05 and a statistical power of 80%. Based on the allelic frequencies of these 100 pairs of mothers and newborns, and given Mendel's laws of genetic transmission (assuming random mating), we estimated the expected proportion of each group of mothers for each polymorphism (LPL*N291S was not considered because it was very rare in this first sample). From the proportion of the smallest group (∼10%), we set our target sample size to 520. Before testing our hypothesis, we examined possible correlations between maternal lipids and all nonlipid and nongenetic (maternal and newborn) factors to identify potential confounders in our subsequent analysis. As previously done by McGladdery and Frohlich (22McGladdery S.H. Frohlich J.J. Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy.J. Lipid Res. 2001; 42: 1905-1912Abstract Full Text Full Text PDF PubMed Google Scholar), we examined how maternal genetic factors alone associated with maternal lipids (as well as other nonlipid parameters) and, by multivariate analysis [analysis of covariance (ANCOVA)], how they interacted with nonlipid factors to determine maternal lipids. Our hypothesis was tested first using a subgroup analysis and then a multivariate analysis. 1) The subgroup analysis was performed by comparing two by two (unpaired two-tailed Student's t-test) the maternal lipids in different groups of mothers classified according to their genetic status and the genetic status of their newborns for each polymorphism separately. 2) ANCOVA was then used to estimate the independent effects of each of the significant (maternal and newborn) genetic factors on maternal lipids. To limit the number of variables, we proceeded first by looking separately at models relating one maternal lipid variable with the polymorphism at one locus in the mothers and the newborns: these models thus included two dummy variables for the presence of the rare allele in the mothers or in the newborns, a product term of these two dummy variables (to assess possible interactions between maternal and newborn genes). We extended these models by adding variables for nongenetic factors that were associated with maternal lipids in our preliminary correlation analysis, and product terms of these last factors with the genetic dummy variables (to assess interactions between nongenetic and genetic factors). Thereafter, we built more general models relating one lipid variable with all of the terms associated (P < 0.10) in these first models, including also product terms to assess the gene-gene interactions between different polymorphisms carried in one or another of the two genomes (mother and newborn) as well as product terms to assess the gene-environment interactions between genetic factors and some nongenetic factors (even if not correlated with maternal lipids in the preliminary correlation analysis) that are commonly described in the general population (e.g., the interaction between weight and LPL*S447X or APOC3*S2 for triglycerides). Because there was no statistically significant interaction (see Results), all final models simplified to additive models as presented in Table 1, where the β-coefficients represented the quantitative estimates of independent lipid changes associated with each factor (genetic and nongenetic) and the changes of R2 estimated the contribution of each factor to the variance of the maternal lipids. These final multivariate models can be easily deduced from Table 1 (column 2); example for maternal LDL-C: LDLm = β0 + β1.Em + β2.Cm + β4.Xm + β5.En + β4.Xn. [X indicates the presence of the X allele of LPL*S447X, C indicates the presence of APOC3*S2, and E indicates the presence of APOE*E2 in mother (m) or in newborn (n).]TABLE 1Multivariate analysis for lipoprotein and apolipoprotein concentrations in the mothersMaternal Genetic Factors OnlyMaternal and Newborn Genetic Factors OnlyMaternal and Newborn Genetic Factors and Newborn LipidsLipidsFactors in the Modelsβ ± SEMR2Pβ ± SEMR2Pβ ± SEMR2PLDL-CMother APOE*E2−29 ± 64.5%<0.001−33 ± 64.5%<0.001 −29 ± 62.9%<0.001Mother APOC3*S2 9 ± 60.5%0.099 ± 60.5%0.0814 ± 51.2%0.007Mother LPL*S447XNS9 ± 50.5%0.0911 ± 50.5%0.03Newborn APOE*E214 ± 61.0%0.0221 ± 61.9%<0.001Newborn LPL*S447X−12 ± 50.7%0.02−9.7 ± 50.6%0.05Newborn LDL-C0.99 ± 0.166.6%<0.001Total R25.0%<0.001Total R27.2%<0.001Total R213.7%<0.001ApoBMother APOE*E2−23 ± 54.9%<0.001−27 ± 54.9%<0.001 −24 ± 54.9%<0.001Mother APOC3*S2 10 ± 41.1%0.0111 ± 41.2%0.00914 ± 41.9%0.001Mother LPL*S447XNS8 ± 40.8%0.0410 ± 41.1%0.01Newborn APOE*E214 ± 51.5%<0.00117 ± 52.2%0.001Newborn LPL*S447X−14 ± 41.8%<0.001 −13 ± 41.5%0.001Newborn LDL-C0.56 ± 0.132.0%0.001Total R26.1%<0.001Total R210.2%<0.001Total R213.6%<0.001HDL-CNewborn weight (kg) −7 ± 22.1%0.001−7 ± 22.1%0.01−7 ± 22.1%<0.001Mother ApoE*E2 6 ± 21.1%0.025 ± 20.9%0.034 ± 10.6%0.05Newborn LPL*S447X5 ± 21.4%0.0065 ± 21.4%0.02Newborn HDL-C0.18 ± 0.091.1%0.01Total R23.2%<0.001Total R24.4%<0.001Total R25.3%<0.001ApoA-INewborn weight (kg) −9 ± 40.8%0.04−9 ± 40.8%0.04−9 ± 40.9%0.04Mother ApoE*E2 13 ± 51.2%0.0213 ± 51.2%0.0112 ± 51.2%0.02Newborn LPL*S447X9 ± 40.9%0.039 ± 40.9%0.04Newborn apoA-I0.26 ± 0.10.8%0.04Total R22.0%0.007Total R22.9%0.002Total R23.8%0.001TriglyceridesMother LPL*S447X−20 ± 9.00.9%0.02Not significant (P = 0,19)Not significant (P = 0,28)Newborn LPL*S447X−21 ± 91.1%0.02 −20 ± 91.1%0.02Newborn LPL*N291S114 ± 312.8%<0.001108 ± 312.8%<0.001Newborn triglyceride0.35 ± 0.20.0080.04Total R20.9%0.02Total R23.9%<0.001Total R24.7%<0.001ApoE, apolipoprotein E; LDL-C, LDL-cholesterol. Open table in a new tab ApoE, apolipoprotein E; LDL-C, LDL-cholesterol. Finally, to exclude the hypothesis that the variations of maternal lipids associated with newborn polymorphisms were associated with these newborn polymorphisms, we examined whether the addition of a variable for the newborn lipid best correlated with the maternal lipid modified the β-coefficients of the final models (Table 1, column 3). All multilinear regression analyses were performed using SPSS for Windows, version 12.0. At the end of our study, we tried to verify the hypothesis that placental apoE (encoded from the fetal genome) was secreted in the maternal circulation by performing apoE phenotyping [isoelectric focusing electrophoresis (IEF) followed by immunoblotting (23Rall S.C. Weisgraber K.H. Mahley R.W. Isolation and characterization of apolipoprotein E.Methods Enzymol. 1986; 128: 273-287Crossref PubMed Scopus (94) Google Scholar, 24Bailleul S. Couderc R. Landais V. Lefevre G. Raichvarg D. Etienne J. Direct phenotyping of human apolipoprotein E in plasma: application to population frequency distribution in Paris (France).Hum. Hered. 1993; 43: 159-165Crossref PubMed Scopus (54) Google Scholar)] in EDTA plasma of eight APOE*E3E3 mothers bearing APOE*E3E2 or APOE*E3E4 newborns. In such cases, the presence of apoE2 or apoE4 in maternal plasma would support the hypothesis. Plasma was analyzed with (23Rall S.C. Weisgraber K.H. Mahley R.W. Isolation and characterization of apolipoprotein E.Methods Enzymol. 1986; 128: 273-287Crossref PubMed Scopus (94) Google Scholar) and without (24Bailleul S. Couderc R. Landais V. Lefevre G. Raichvarg D. Etienne J. Direct phenotyping of human apolipoprotein E in plasma: application to population frequency distribution in Paris (France).Hum. Hered. 1993; 43: 159-165Crossref PubMed Scopus (54) Google Scholar) neuraminidase treatment. IEF was performed under the classical conditions for optimal apoE isoform separation (23Rall S.C. Weisgraber K.H. Mahley R.W. Isolation and characterization of apolipoprotein E.Methods Enzymol. 1986; 128: 273-287Crossref PubMed Scopus (94) Google Scholar). Immunoblotting was assayed using two different human apoE antibodies [mouse monoclonal and goat polyclonal antibodies from Calbiochem (La Jolla, CA)] followed by anti-mouse or anti-goat IgG conjugated with peroxidase. The detection limit of our method was examined by testing a mix of pooled plasma of E3E3 mothers with E3E3 newborns (diluted at 1:2) in which we added different dilutions (final dilutions of 1:2, 1:4, 1:8, 1:10, 1:20, and 1:40) of cord plasma of newborns with E3/E4 or E2/E3. In these mixes, we found that the E2 or E4 bands of newborn plasma were still visible at the 1:8 final dilution but not at higher dilutions. The characteristics of our cohort of 525 mothers and newborns (261 girls and 264 boys) have been described previously (15Descamps O.S. Bruniaux M. Guilmot P.F. Tonglet R. Heller F.R. Lipoprotein concentrations in newborns are associated with allelic variations in their mothers.Atherosclerosis. 2004; 172: 287-298Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Briefly, maternal characteristics were as follows: age, 28.8 ± 5.3 years; height, 162.8 ± 6.1 cm; weight at the end of pregnancy, 78.9 ± 15.4 kg; 19% smoked regularly during the whole pregnancy. In 421 women, prepregnancy weight was known (279 self-reported retrospectively and 142 recorded in file: 65.9 ± 16.3 kg) and weight gain was calculated: 12.8 ± 5.1 kg. Lipid concentrations in mothers (in mg/dl) were as follows: total cholesterol, 297 ± 52; LDL-C, 162 ± 47; HDL-C, 83 ± 18; triglycerides, 258 ± 82; apoA-I, 225 ± 39; and apoB, 151 ± 35. Newborn characteristics were as follows: gestational age, 39.3 ± 1.1 weeks; newborn weight, 3,230 ± 412 g; newborn height, 49.0 ± 2.6 cm; and head circumference, 34.0 ± 1.4 cm. Lipid concentrations in newborns (in mg/dl) were as follows: total cholesterol, 72 ± 16; LDL-C, 29 ± 13; HDL-C, 34 ± 9; triglycerides, 43 ± 19; apoA-I, 77 ± 13; and apoB, 28 ± 9. Among all of the maternal (age, weight before and at the end of pregnancy, weight gain, and smoking status) and newborn (sex, gestational age, weight, height, head circumference, and body mass index) nonlipid variables, only newborn weight was correlated with maternal HDL-C (r = −0.15, P = 0.001) and less with maternal apoA-I (r = −0.09, P = 0.07). This absence of correlation was not surprising given the very weak level (or the absence) of such correlations in the literature (22McGladdery S.H. Frohlich J.J. Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy.J. Lipid Res. 2001; 42: 1905-1912Abstract Full Text Full Text PDF PubMed Google Scholar, 25Spellacy W.N. Ashbacher F.L.V. Harris G.K. Buhi W.C. Total cholesterol content in maternal and umbilical vessels in term pregnancies.Obstet. Gynecol. 1974; 44: 661-665PubMed Google Scholar, 26Jimenez D.M. Pocovi M. Ramon-Cajal J. Romero M.A. Martinez H. Grande F. Longitudinal study of plasma lipids and lipoprotein cholesterol in normal pregnancy and puerperium.Gynecol. Obstet. Invest. 1988; 25: 158-164Crossref PubMed Scopus (49) Google Scholar, 27Peterson C.M. Jovanovic-Peterson L. Mills J.L. Conley M.R. Knopp R.H. Reed G.F. Aarons J.H. Holmes L.B. Brown Z. Allen M. Van et al.The Diabetes in Early Pregnancy Study: changes in cholesterol, triglycerides, body weight, and blood pressure. The National Institute of Child Health and Human Development—the Diabetes in Early Pregnancy Study.Am. J. Obstet. Gynecol. 1992; 166: 513-518Abstract Full Text PDF PubMed Scopus (28) Google Scholar) and given the narrow range of variations of maternal age, gestational age, and newborn weight attributable to our selection process. As described previously (15Descamps O.S. Bruniaux M. Guilmot P.F. Tonglet R. Heller F.R. Lipoprotein concentrations in newborns are associated with allelic variations in their mothers.Atherosclerosis. 2004; 172: 287-298Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar), maternal lipids correlated slightly with newborn lipids, the best correlations being between newborn and maternal LDL (R = 0.26, R2 = 6.7%, P < 0.001), between newborn and mate" @default.
• W1982393747 created "2016-06-24" @default.
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• W1982393747 title "Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children" @default.
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