Placental FTO expression relates to fetal growth

Bassols, Judit; Prats‐Puig, Anna; Vázquez-Ruíz, Montserrat; García-González, María Mar; Martínez-Pascual, María; Avellí, P.; Martínez-Martínez, Ricardo; Fàbrega, R.; Colomer-Virosta, C.; Soriano-Rodríguez, Pilar; Díaz, Marta; Zegher, Francis de; Ibáñez, Lourdes; López‐Bermejo, Abel

doi:10.1038/ijo.2010.62

Cited by 33 publications

(39 citation statements)

References 31 publications

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“…The results indicate that genetic variations in FTO do not have a strong main eVect in the modulation of birth weight, which is consistent with GWAS that has P value >0.2 for rs9939609 (Frayling et al 2007). A recent study (Bassols et al 2010) has shown that FTO was highly expressed in the placenta, and was associated with increased birth weight. This inconsistent Wnding suggests that FTO eVects may depend on expressed tissue.…”

Section: Discussionsupporting

confidence: 70%

FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

et al. 2010

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SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI). However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658 white subjects from childhood (3-17 years) to adulthood (18-45 years). No significant associations of FTO SNPs with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs (rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10(-5), 2.0 × 10(-4) and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity.

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Section: Discussionsupporting

confidence: 70%

FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

et al. 2010

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“…Four of the five CpG loci associated with placental Mn are of crucial importance in central nervous system differentiation and development ( EMX2OS 43 , ATAD2B 44 and EN1 45 ) and, when expressed in the placenta, fetal growth ( FTO 46 ). Moreover, a well-characterized link exists between FTO and obesity 46 .…”

Section: 1 Discussionmentioning

confidence: 99%

“…Moreover, a well-characterized link exists between FTO and obesity 46 . EN1 is a homeobox gene 45 , underscoring its importance in development.…”

Section: 1 Discussionmentioning

confidence: 99%

DNA methylation changes in the placenta are associated with fetal manganese exposure

Maccani

Koestler

Houseman

et al. 2015

Reproductive Toxicology

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Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina’s HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p=0.045). 713 loci were associated with Mn exposure (p<0.0001). 5 significantly differentially-methylated (p<1.3×10−7) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44 grams. Our observations suggests a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation.

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“…As the correct fetal development is based on the DNA-methylation-based programming, in theory the FTO gene is a promising candidate gene for predisposition to spontaneous abortion. The potential role of FTO in fetal development is further supported by the finding that in humans, FTO is highly expressed in placenta and its expression appears to correlate with increased fetal weight and length (5).…”

Section: Sirmentioning

confidence: 92%

FTO gene variant and risk of spontaneous abortion

Hubacek

Kasparova

Dlouhá

et al. 2015

Acta Obstet Gynecol Scand

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Sir,We read with interest the study of Andraweera et al., published recently in Acta Obstetricia et Gynecologica Scandinavica (1), reporting a strong association between maternal FTO (rs9939609) genotype and the risk of miscarriage and recurrent pregnancy loss. Inspired by the report, we attempted to test a related hypothesis that the FTO polymorphism is associated with spontaneous abortions when tissue sample from aborted fetus is used instead of maternal DNA. Such an association would indirectly confirm the findings by Andraweera et al. (1).We compared 457 tissue samples of spontaneous abortions during the first trimester (cases) with a general population sample of 6681 middle-aged adults (aged 45-69 years) used as controls (2). All cases and controls were genotyped for the FTO rs17817449 polymorphism; this single nucleotide polymorphism is in almost complete linkage disequilibrium with neighboring rs9939609. No association between number of children and FTO genotype was detected among controls.The distribution of the FTO genotypes did not differ between the cases and controls. The frequencies for GG vs. GT vs. TT alleles were 19.9% vs. 46.8% vs. 33.3% in cases and 19.3% vs. 47.7% vs. 32.9% among controls (P = 0.92). The odds ratio for GG vs. GT/TT carriers was 1.04 (95% CI 0.82-1.32; P = 0.75).The FTO gene was first identified by a genome-wide association study as an independent genetic risk factor for obesity (3); more recently, the polymorphism has also been implicated in other conditions, such as diabetes mellitus, myocardial infarction, renal failure or cancer. However, the exact biological role of the FTO gene remains unclear (4). The gene is involved in demethylation of nucleic acids. As the correct fetal development is based on the DNA-methylation-based programming, in theory the FTO gene is a promising candidate gene for predisposition to spontaneous abortion. The potential role of FTO in fetal development is further supported by the finding that in humans, FTO is highly expressed in placenta and its expression appears to correlate with increased fetal weight and length (5).The fact that our study did not find any difference in FTO genotype between spontaneous abortions and healthy adults may be due to at least two reasons. First, the geographical localization and ethnic composition of our study sample differs from that in the study by Andraweera et al. (1). Second, there was a major difference in the selection of cases between the studies. Our study has focused on analysis of aborted fetal tissues, not on females with experience of pregnancy loss. It is possible that the methylation status and subsequent fetal development depends on the genetic characteristics/FTO variant of females with a history of recurrent pregnancy loss, rather than on characteristics of the fetus. On the other hand, one would expect that even if the main risk factor is maternal genotype it would be detected in studies using fetal DNA (as it reflects the genotype inherited from the mother). Further studies are needed to confirm o...

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Placental FTO expression relates to fetal growth

Cited by 33 publications

References 31 publications

FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

DNA methylation changes in the placenta are associated with fetal manganese exposure

FTO gene variant and risk of spontaneous abortion

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