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Functional SOCS1 polymorphisms are associated with variation in obesity in whites

Gylvin, T.; Ek, J.; Nolsoe, R.; Albrechtsen, A.; Andersen, G.; Bergholdt, R.; Brorsson, C.; Bang-Berthelsen, C. H.; Hansen, T. and Karlsen, A E, et al. (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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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
ISSN
1462-8902
DOI
10.1111/j.1463-1326.2008.00900.x
language
English
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yes
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a38de4a4-b2b9-4f54-8616-0999ce1fc3fb (old id 1312251)
date added to LUP
2010-12-23 10:37:40
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2017-10-29 03:41:11
@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},
  keyword      = {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},
  volume       = {11},
  year         = {2009},
}