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Evaluation of A2BP1...
Evaluation of A2BP1 as an Obesity Gene
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
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2010-08-19
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American Diabetes Association,2010
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:7f976ac1-a0da-44e2-b7fa-61d4383d3c02
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https://lup.lub.lu.se/record/1752218URI
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https://doi.org/10.2337/db09-1604DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-41435URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS-Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392) (Meyre et al. Nat Genet 2009;41:157-159). Selected variants were genotyped in two additional samples of Caucasians (Amish, n = 1,149, and German children case/control subjects, n = 998) and one additional Native American (n = 2,531) sample. Small interfering RNA was used to knockdown A2bp1 message levels in mouse embryonic hypothalamus cells. RESULTS-No single variant in A2BP1 was reproducibly associated with obesity across the different populations. However, different variants within intron 1 of A2BP1 were associated with BMI in full-heritage Pima Indians (rs10500331, P = 1.9 x 10(-7)) and obesity in French Caucasian adult (rs4786847, P = 1.9 x 10(-10)) and children (rs8054147, P = 9.2 x 10(-6)) case/control subjects. Reduction of A2bp1 in mouse embryonic hypothalamus cells decreased expression of Atxn2, Insr, and Mc4r. CONCLUSIONS-Association analysis suggests that variation in A2BP1 influences obesity, and functional studies suggest that A2BP1 could potentially affect adiposity via the hypothalamic MC4R pathway. Diabetes 59:2837-2845, 2010
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Hanson, Robert L.
(författare)
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Traurig, Michael T.
(författare)
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Muller, Yunhua L.
(författare)
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Kaur, Bakhshish P.
(författare)
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Perez, Jessica M.
(författare)
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Meyre, David
(författare)
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Fu, Mao
(författare)
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Koerner, Antje
(författare)
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Franks, PaulLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Clinical Research Center, Malmö General Hospital, Lund University, Malmö, Sweden(Swepub:umu)pafr0003
(författare)
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Kiess, Wieland
(författare)
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Kobes, Sayuko
(författare)
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Knowler, William C.
(författare)
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Kovacs, Peter
(författare)
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Froguel, Philippe
(författare)
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Shuldiner, Alan R.
(författare)
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Bogardus, Clifton
(författare)
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Baler, Leslie J.
(författare)
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Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes: American Diabetes Association59:11, s. 2837-28451939-327X0012-1797
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Diabetes
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Ma, Lijun
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Hanson, Robert L ...
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Traurig, Michael ...
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Muller, Yunhua L ...
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Kaur, Bakhshish ...
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Perez, Jessica M ...
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visa fler...
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Meyre, David
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Fu, Mao
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Koerner, Antje
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Franks, Paul
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Kiess, Wieland
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Kobes, Sayuko
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Knowler, William ...
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Kovacs, Peter
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Froguel, Philipp ...
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Shuldiner, Alan ...
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Bogardus, Clifto ...
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Baler, Leslie J.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
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Diabetes
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Lunds universitet
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