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Functional SOCS1 po...
Functional SOCS1 polymorphisms are associated with variation in obesity in whites
- Article/chapterEnglish2009
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LIBRIS-ID:oai:lup.lub.lu.se:a38de4a4-b2b9-4f54-8616-0999ce1fc3fb
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https://lup.lub.lu.se/record/1312251URI
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https://doi.org/10.1111/j.1463-1326.2008.00900.xDOI
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Language:English
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Summary in:English
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The suppressor of cytokine signalling 1 (SOCS1) is a natural inhibitor of cytokine and insulin signalling pathways and may also play a role in obesity. In addition, SOCS1 is considered a candidate gene in the pathogenesis of both type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective was to perform mutation analysis of SOCS1 and to test the identified variations for association to T2D-related quantitative traits, T2D or T1D. Mutation scanning was performed by direct sequencing in 27 white Danish subjects. Genotyping was carried out by TaqMan allelic discrimination. A total of more than 8100 individuals were genotyped. Eight variations were identified in the 5' untranslated region (UTR) region. Two of these had allele frequencies below 1% and were not further examined. The six other variants were analysed in groups of T1D families (n = 1461 subjects) and T2D patients (n = 1430), glucose tolerant first-degree relatives of T2D patients (n = 212) and normal glucose tolerant (NGT) subjects. The rs33977706 polymorphism (-820G > T) was associated with a lower body mass index (BMI) (p = 0.004). In a second study (n = 4625 NGT subjects), significant associations of both the rs33977706 and the rs243330 (-1656G > A) variants to obesity were found (p = 0.047 and p = 0.015) respectively. The rs33977706 affected both binding of a nuclear protein to and the transcriptional activity of the SOCS1 promoter, indicating a relationship between this polymorphism and gene regulation. This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.
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Ek, J.
(author)
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Nolsoe, R.
(author)
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Albrechtsen, A.
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Andersen, G.
(author)
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Bergholdt, R.
(author)
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Brorsson, C.
(author)
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Bang-Berthelsen, C. H.
(author)
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Hansen, T.
(author)
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Karlsen, A E
(author)
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Billestrup, N.
(author)
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Borch-Johnsen, K.
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Jorgensen, T.
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Pedersen, O.
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Mandrup-Poulsen, T.
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Nerup, JörnLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)extLU-131
(author)
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Pociot, FlemmingLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine(Swepub:lu)extLU-58
(author)
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Institutionen för kliniska vetenskaper, LundMedicinska fakulteten
(creator_code:org_t)
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In:Diabetes, Obesity and Metabolism: Wiley11:3, s. 196-2031462-89021463-1326
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Gylvin, T.
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Ek, J.
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Nolsoe, R.
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Albrechtsen, A.
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Andersen, G.
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Bergholdt, R.
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Brorsson, C.
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Bang-Berthelsen, ...
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Hansen, T.
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Karlsen, A E
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Billestrup, N.
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Borch-Johnsen, K ...
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Jorgensen, T.
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Pedersen, O.
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Mandrup-Poulsen, ...
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Nerup, Jörn
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Pociot, Flemming
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- MEDICAL AND HEALTH SCIENCES
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Lund University