Effects of FTO and PPAR? variants on intrauterine growth restriction in a Brazilian birth cohort.

摘要

Background: Recently, associations of genetic variants with birth weight and adult conditions such as type 2 diabetes, blood pressure and height have been described. This context leads to the hypothesis that genes linked to obesity and metabolic disorders in later life, such as the FTO (Fat Mass and Obesity Associated) and PPARγ (Peroxisome Proliferator-Activated Receptor) genes, may play a role both in intrauterine development and in the genesis of obesity later in life. The objective of this study is to evaluate the association of FTO and PPARγ SNPs (Single Nucleotide Polymorphism) with intrauterine growth restriction (IUGR) in a Brazilian cohort, taking into account maternal factors also related to IUGR. Methods: This was a case-control study nested in a prospective birth cohort in Ribeir?o Preto, Brazil. Participants were evaluated at birth and at adult age. At birth all 6827 mothers were recruited in hospitals in the city and a sample of 2063 of their offsprings were interviewed at 23-25 years of age, when a blood sample was collected for DNA extraction and genotyping. All 280 participants defined as having IUGR according to the birth weight ratio (BWR), which is the ratio between the child's weight and the median weight for gestational age according to a reference curve, being restricted those with BWR ≤ 0.85, and a random sample of 276 non-IUGR participants were studied. Odds ratios (OR) and 95% confidence intervals (95% CI) for the association between FTO and PPARγ genes were estimated by unadjusted and further adjusted logistic regression analyses, separately according to sex. Results: There was a protective effect of the FTO gene on IUGR only for males, and the PPARγ gene was positively associated with IUGR for both males and females. Males carrying the TA genotype of the FTO rs9939609 were significantly protected against IUGR (OR = 0.47, 95% CI 0.26-0.86), when compared to the TT genotype, whilst AA genotype was not associated with IUGR (p > 0.05). For the PPARγ gene, the AG genotype of rs41516544 showed a high risk for IUGR both for males (OR = 27.83, 95% CI 3.65-212.32) and females (OR = 8.94, 95% CI 1.96-40.88), when compared to the AA genotype. Conclusions: Genetic variations in the FTO and PPARγ genes, which are known to be associated with obesity and metabolic disorders in later life, seem to have association also with IUGR, in a different way for males and females. We can speculate that these genes may play a role in the association of IUGR with metabolic conditions later in life.