Functional SOCS1 polymorphisms are associated with variation in obesity in whites
(2009) In Diabetes, Obesity and Metabolism 11(3). p.196-203- Abstract
- 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... (More)
- 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. (Less)
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- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- promoter activity, SOCS, obesity, insulin, EMSA, cytokines, diabetes
- in
- Diabetes, Obesity and Metabolism
- volume
- 11
- issue
- 3
- pages
- 196 - 203
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000262781500003
- scopus:59349092716
- pmid:19215277
- ISSN
- 1462-8902
- DOI
- 10.1111/j.1463-1326.2008.00900.x
- language
- English
- LU publication?
- yes
- id
- a38de4a4-b2b9-4f54-8616-0999ce1fc3fb (old id 1312251)
- date added to LUP
- 2016-04-01 12:25:36
- date last changed
- 2022-05-14 22:11:34
@article{a38de4a4-b2b9-4f54-8616-0999ce1fc3fb,
abstract = {{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.}},
author = {{Gylvin, T. and Ek, J. and Nolsoe, R. and Albrechtsen, A. and Andersen, G. and Bergholdt, R. and Brorsson, C. and Bang-Berthelsen, C. H. and Hansen, T. and Karlsen, A E and Billestrup, N. and Borch-Johnsen, K. and Jorgensen, T. and Pedersen, O. and Mandrup-Poulsen, T. and Nerup, Jörn and Pociot, Flemming}},
issn = {{1462-8902}},
keywords = {{promoter activity; SOCS; obesity; insulin; EMSA; cytokines; diabetes}},
language = {{eng}},
number = {{3}},
pages = {{196--203}},
publisher = {{Wiley-Blackwell}},
series = {{Diabetes, Obesity and Metabolism}},
title = {{Functional SOCS1 polymorphisms are associated with variation in obesity in whites}},
url = {{http://dx.doi.org/10.1111/j.1463-1326.2008.00900.x}},
doi = {{10.1111/j.1463-1326.2008.00900.x}},
volume = {{11}},
year = {{2009}},
}