Abstract
Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.
Highlights
Intrauterine growth restriction (IUGR) is known to be related to a higher risk of neonatal mortality, minor cognitive deficits, school problems, metabolic syndrome (MetS), and cardiovascular disease in adulthood [1,2,3,4]. the consequences of IUGR have been widely reported, causal explanations are still unclear
In addition to suggestions about the importance of maternal, fetal, placental, and genetic factors or any combination thereof [5,6], other hypotheses have been proposed, among them: 1) the Barker hypothesis, which suggests that the maternal uterine environment in pregnancy has long-term effects in adulthood resulting in increased metabolic disease and diabetes risk [1,7]; 2) the fetal insulin hypothesis, which proposes that the insulin secreted by the fetal pancreas in response to the maternal glucose concentration affects both newborn size and predisposition to adult diseases [8]; and 3) the genetic factors hypothesis, which is supported by the observation that IUGR tends to cluster in families and recur in successive pregnancies [9,10]
Higher differences in genotype and allele distributions between IUGR and non-IUGR groups were observed for the heterozygous genotypes AG and CT of PPARg single-nucleotide polymorphisms (SNPs), rs41516544 and rs3856806
Summary
Intrauterine growth restriction (IUGR) is known to be related to a higher risk of neonatal mortality, minor cognitive deficits, school problems, metabolic syndrome (MetS), and cardiovascular disease in adulthood [1,2,3,4]. the consequences of IUGR have been widely reported, causal explanations are still unclear. In addition to suggestions about the importance of maternal, fetal, placental, and genetic factors or any combination thereof [5,6], other hypotheses have been proposed, among them: 1) the Barker hypothesis, which suggests that the maternal uterine environment in pregnancy has long-term effects in adulthood resulting in increased metabolic disease and diabetes risk [1,7]; 2) the fetal insulin hypothesis, which proposes that the insulin secreted by the fetal pancreas in response to the maternal glucose concentration affects both newborn size and predisposition to adult diseases [8]; and 3) the genetic factors hypothesis, which is supported by the observation that IUGR tends to cluster in families and recur in successive pregnancies [9,10] In this regard, a number of singlenucleotide polymorphisms (SNPs) in genes involved in the efficiency of the metabolism of specific macronutrients may have a relevant role for adult MetS in different populations [11,12,13]. Several allelic variants of the PPARg gene (peroxisome proliferator-activated receptor-gamma) have
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