RESUMEN
BACKGROUND: Low weight at birth is associated with obesity in later life. One hypothesis to explain such an association is that genetic variants that increase the risk of obesity also reduce fetal weight. Recently, obesity in adults was found to be associated with common variants of the fat mass and obesity-associated (FTO) gene. We examined the association between FTO polymorphisms and birth weight in a singleton, full-term birth cohort of 494 newborn-mother pairs without any complications. RESULTS: The risk alleles for obesity ("A" allele for the rs9939609 FTO variant and "G" allele for the rs9930506 FTO variant) were associated with low weight at birth. The mean differences per risk allele were -79 g (95% CI: -129 to -30; p = 0.002) for rs9939609 and -84 g (95% CI: -131 to -36; P < 0.001) for rs9930506. The level of association remained statistically significant after adjustment for the maternal risk allele and for variables usually associated with birth weight (-50 g, 95% CI: -99 to 0; p = 0.05 for rs9939609 and -48 g, 95% CI: -100 to 0; p = 0.05 for rs9930506). In the follow-up, the allelic difference in weight was attenuated over time. CONCLUSIONS: The FTO variants that confer a predisposition to obesity later in life appear to be associated with low weight at birth. This finding favors the hypothesis of a common genetic denominator that predisposes to a low weight at birth and obesity in adults.
Asunto(s)
Peso al Nacer/genética , Proteínas/genética , Adulto , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Obesidad/genética , Polimorfismo de Nucleótido Simple , Riesgo , Adulto JovenRESUMEN
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).
Asunto(s)
Lipoproteínas/metabolismo , Polimorfismo Genético , Adulto , Apolipoproteína C-III , Apolipoproteínas C/genética , Apolipoproteínas E/genética , Colesterol/metabolismo , LDL-Colesterol/sangre , Femenino , Frecuencia de los Genes , Genoma Humano , Humanos , Recién Nacido , Lípidos/química , Lipoproteínas/química , Masculino , Análisis Multivariante , Fenotipo , Placenta/metabolismo , Embarazo , Complicaciones Cardiovasculares del Embarazo , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Factors determining lipoprotein concentrations in the fetus are not yet fully understood. We postulated that an important factor is the genetic make-up of the mother. In the present study, we examined the associations between the cord blood concentrations of lipoproteins of 525 newborns and the polymorphisms present in their mothers on the genes of apolipoprotein E (APOE*E2, *E3, *E4), apolipoprotein C-III (APOC3*C3238G also called APOC3*S2) and lipoprotein lipase (LPL*S447X). RESULTS: Newborns born of mothers with APOE*E2 allele had significantly lower cord blood LDL-C (P < 0.01) and apoB (P < 0.01) and significantly higher cord blood HDL-C and apoA1 (all P-values < 0.03) compared to those born of mothers with APOE*E3E3 genotype. These associations were independent of the presence of APOE*E2 allele in the newborns. Similarly, APOC3*S2 in mothers was associated with significantly lower (all P < 0.001) cord blood LDL-C, apoB, HDL-C and apoA1. In contrast, LPL*S447X in mothers lowered significantly cord blood LDL-C and apoB only when LPL*S447X was present in newborns. Most of the effects of these maternal polymorphisms on the newborns were independent of the changes of maternal lipoproteins generated by these polymorphisms. CONCLUSIONS: This is the first evidence that maternal genetic variations influence fetal lipoprotein concentrations, independent of the genetic status of the fetus and of the variations of maternal lipoprotein concentrations generated by these genetic variants. It suggests that proteic components of maternal lipoproteins strongly control the metabolism of maternal lipoproteins carried out at the surface of the placenta to assure the cholesterol delivery to the fetus.