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dc.contributor.authorTuncman, G.
dc.contributor.authorErbay, E.
dc.contributor.authorHom, X.
dc.contributor.authorVivo, I. De
dc.contributor.authorCampos, H.
dc.contributor.authorRimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600
dc.contributor.authorHotamisligil, G. S.
dc.date.accessioned2019-08-27T18:05:27Z
dc.date.issued2006
dc.identifier.citationTuncman, G., E. Erbay, X. Hom, I. De Vivo, H. Campos, E. B. Rimm, and G. S. Hotamisligil. 2006. “A Genetic Variant at the Fatty Acid-Binding Protein aP2 Locus Reduces the Risk for Hypertriglyceridemia, Type 2 Diabetes, and Cardiovascular Disease.” Proceedings of the National Academy of Sciences 103 (18): 6970–75. https://doi.org/10.1073/pnas.0602178103.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41263036*
dc.description.abstractObesity and the associated pathologies including dyslipidemia, insulin resistance, type 2 diabetes, and cardiovascular disease constitute a major threat to global human health. Yet, the genetic factors that differentially predispose individuals to this cluster of pathologies are unclear. The fatty acid-binding protein aP2 is a cytoplasmic lipid chaperon expressed in adipocytes and macrophages. Mice with aP2 deficiency are partially resistant to obesity-induced insulin resistance and type 2 diabetes, have lower circulating triglycerides, and exhibit marked protection against atherosclerosis. Here, we demonstrate a functionally significant genetic variation at the aP2 locus in humans that results in decreased adipose tissue aP2 expression due to alteration of the CAAT box/enhancer-binding protein binding and reduced transcriptional activity of the aP2 promoter. In population genetic studies with 7,899 participants, individuals that carry this T-87C polymorphism had lower serum triglyceride levels and significantly reduced risk for coronary heart disease and type 2 diabetes compared with subjects homozygous for the WT allele. Taken together, our results indicate that reduction in aP2 activity in humans generate a metabolically favorable phenotype that is similar to aP2 deficiency in experimental models.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleA genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorRimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600
dc.date.available2019-08-27T18:05:27Z
dash.workflow.comments1Science Serial ID 89872
dc.identifier.doi10.1073/pnas.0602178103
dash.source.volume103;18
dash.source.page6970


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