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      • Poster Session : PS 0458 ; Genetics ; Replication of the Association Between the FTORs9939609 Polymorphism and Methylation Patterns of the FTO Gene in Two Mediterranean Populations

        ( Carolina Ortega Azorin ),( Josev Sorli ),( Diego Godoy ),( Olga Portoles ),( Eva M Asensio ),( Oscar Coltell ),( Dolores Corella ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: Dysregulation of DNA methylation has been related with obesity. Although the association of the FTO-rs9939609-T>A polymorphism with obesity has been widely reported, few studies have analyzed the methylation patterns associated with this polymorphism. Moreover, replication of the individual fi nding is needed to increase the evidence level. We aimed to analyze the association between methylation levels in selected CpG island of the FTO gene and the rs9939609 polymorphism in two populations. Methods: We studied 195(98 men and 97 women) subjects participating in the PREDIMED-Valencia study, and 46 subjects (23 men and 23 women) of the general population participating in the OBENUTIC study.DNA was obtained from leucocytes. The rs9939609 polymorphism was determined and quantitative DNA methylation analysis of the FTO gene was undertaken by matrix-assisted laser desorption ionization-time of fi ight (MALDI-TOF) mass spectrometry. We evaluated methylation levels in 21 CpG sites (13 in amplicon A and 8 in amplicon B) surrounding the rs9939609 polymorphim in intron 1 the FTO(Chr16:53817859-53822719). Results: Participants in the PREDIMED were older than participants in the OBENUTIC study. We detected significant differences in the methylation of several CpG sites between these populations, with PREDIMED participants having higher methylation levels. Interestingly, we observed that the CpG site 8 in amplicon A was differentially methylated depending on the FTO-rs9939609 polymorphism, where homozygous for the obesity-risk allele (AA) had lower methylation levels in both populations (expressed as % of methylated C:PREDIMED:44.5±39.2% in TT,19.4±26.8% in TA and 4.9±11.7% in AA;P<0.001;OBENUTIC:12.9±17.3% in TT,4.2±8.3% in TA and 0.0±0.0% in AA;P=0.046). Conclusions: We detected differences in methylation of CpG sites of FTO gene in high cardiovascular risk subjects. We also replicated the association between the rs9939609 polymorphism and methylation levels in both populations.

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