Effects of FTO and PPARγ variants on intrauterine growth restriction in a Brazilian birth cohort

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 obesityassociated) and PPARg (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 PPARg (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 PPARg rs41516544 increased the risk of IUGR for male offspring (OR 27.83,) 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 PPARg SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.

FTO: a critical role in obesity and obesity-related diseases

“…Among the pregnant women, the maternal and infant AA genotype of the obesity associated FTO rs9939609 SNP associates with increased risk for small for gestational age pregnancy (SGA) and spontaneous preterm birth (sPTB), the SNP might play a significant role in calculating the risk of pregnancy complications and subsequent vascular diseases [29] . FTO rs9939609 TA genotype only related with the risk reduction of intrauterine growth restriction (IUGR) in male offspring [30] .…”

Genetic Background of Fetal Growth Restriction

“…Barbieri et al 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 FGR in a Brazilian birth cohort. They revealed that PPARγ SNP was positively correlated and FTO SNP negatively correlated with FGR, and these effects were gender specific [ 31 ]. Karimi-Zarchi et al suggested that the Apa1 polymorphism of insulin growth factor 2 (IGF-2) is associated with an increased risk of FGR [ 32 ].…”