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Functional SOCS1 polymorphisms are associated with variation in obesity in whites.
- Source :
- Diabetes, Obesity & Metabolism; Mar2009, Vol. 11 Issue 3, p196-203, 8p, 1 Black and White Photograph, 4 Charts, 1 Graph
- Publication Year :
- 2009
-
Abstract
- Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population. [ABSTRACT FROM AUTHOR]
- Subjects :
- GENETIC polymorphisms
OBESITY
CYTOKINES
HYPOGLYCEMIC agents
CELLULAR immunity
Subjects
Details
- Language :
- English
- ISSN :
- 14628902
- Volume :
- 11
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Diabetes, Obesity & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 36244167
- Full Text :
- https://doi.org/10.1111/j.1463-1326.2008.00900.x