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dc.contributor.authorFriedman, David J.
dc.contributor.authorTalbert, Matthew E.
dc.contributor.authorBowden, Donald W.
dc.contributor.authorFreedman, Barry I.
dc.contributor.authorMukanya, Yves
dc.contributor.authorEnjyoji, Keiichi
dc.contributor.authorRobson, Simon Christopher
dc.date.accessioned2011-11-16T17:38:59Z
dc.date.issued2008
dc.identifier.citationFriedman, David J., Matthew E. Talbert, Donald W. Bowden, Barry I. Freedman, Yves Mukanya, Keiichi Enjyoji, and Simon C. Robson. 2009. Functional ENTPD1 polymorphisms in African Americans With diabetes and end-stage renal disease. Diabetes 58(4): 999-1006.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5346717
dc.description.abstractObjective: The vascular ectonucleotidase ENTPD1 protects against renal injury and modulates glucose homeostasis in mouse models. We sought to determine whether human variation in ENTPD1 influences predisposition to diabetes or diabetic nephropathy. Research Design and Methods: We analyzed ENTPD1 single nucleotide polymorphisms (SNPs) in 363 African American control subjects, 380 subjects with type 2 diabetes and end-stage renal disease (DM-ESRD), and 326 subjects with ESRD unrelated to diabetes (non–DM-ESRD). Using human cell lines, we correlated disease-associated ENTPD1 haplotypes with ENTPD1 gene expression. Finally, we studied consequences of ENTPD1 deletion in a mouse model of type 2 diabetes (db/db). Results: A common ENTPD1 two-SNP haplotype was associated with increased risk for DM-ESRD (P = 0.0027), and an uncommon four-SNP haplotype was associated with protection against DM-ESRD (P = 0.004). These haplotypes correlated with ENTPD1 gene expression levels in human cell lines in vitro. Subjects with high ENTPD1-expressing haplotypes were enriched in the DM-ESRD group. By crossing ENTPD1-null mice with db mice, we show that ENTPD1 deletion has prominent effects on metabolic syndrome traits. Specifically, deletion of ENTPD1 lowered glucose levels in control (db/−) mice with one functional leptin receptor and dramatically lowered weights in db/db mice with no functional leptin receptors. Similar effects were seen in aged ENTPD1-null mice with normal leptin receptors. Conclusions: ENTPD1 polymorphisms appear to influence susceptibility to type 2 diabetes and/or diabetic nephropathy in African Americans. Studies in human cell lines and in vivo mouse data support a potential role for ENTPD1 genetic variation in susceptibility to type 2 diabetes.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi://10.2337/db08-1214en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661602/pdf/en_US
dash.licenseLAA
dc.subjectgeneticsen_US
dc.titleFunctional ENTPD1 Polymorphisms in African Americans With Diabetes and End-Stage Renal Diseaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorFriedman, David J.
dc.date.available2011-11-16T17:38:59Z
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dc.identifier.doi10.2337/db08-1214*
dash.contributor.affiliatedFriedman, David
dash.contributor.affiliatedRobson, Simon


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