Functional SOCS1 polymorphisms are associated with variation in obesity in whites

T Gylvin; J Ek; R. Nolsøe; A. Albrechtsen; G Andersen; R. Bergholdt; C Brorsson; C. H. Bang-Berthelsen; T. Hansen; A. E. Karlsen; N Billestrup; K Borch-Johnsen; Torben Jørgensen; Oluf Pedersen; T Mandrup-Poulsen; J. Nerup; Flemming Michael Pociot

doi:10.1111/j.1463-1326.2008.00900.x

Functional SOCS1 polymorphisms are associated with variation in obesity in whites

T Gylvin, J Ek, R. Nolsøe, A. Albrechtsen, G Andersen, R. Bergholdt, C Brorsson, C. H. Bang-Berthelsen, T. Hansen, A. E. Karlsen, N Billestrup, K Borch-Johnsen, Torben Jørgensen, Oluf Pedersen, T Mandrup-Poulsen, J. Nerup, Flemming Michael Pociot

19 Citations (Scopus)

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.

Original language	English
Journal	Diabetes, Obesity and Metabolism
Volume	11
Issue number	3
Pages (from-to)	196-203
Number of pages	7
ISSN	1462-8902
DOIs	https://doi.org/10.1111/j.1463-1326.2008.00900.x
Publication status	Published - 2009

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10.1111/j.1463-1326.2008.00900.x

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Gylvin, T., Ek, J., Nolsøe, R., Albrechtsen, A., Andersen, G., Bergholdt, R., Brorsson, C., Bang-Berthelsen, C. H., Hansen, T., Karlsen, A. E., Billestrup, N., Borch-Johnsen, K., Jørgensen, T., Pedersen, O., Mandrup-Poulsen, T., Nerup, J., & Pociot, F. M. (2009). Functional SOCS1 polymorphisms are associated with variation in obesity in whites. Diabetes, Obesity and Metabolism, 11(3), 196-203. https://doi.org/10.1111/j.1463-1326.2008.00900.x

Gylvin, T, Ek, J, Nolsøe, R, Albrechtsen, A, Andersen, G, Bergholdt, R, Brorsson, C, Bang-Berthelsen, CH, Hansen, T, Karlsen, AE, Billestrup, N, Borch-Johnsen, K, Jørgensen, T, Pedersen, O , Mandrup-Poulsen, T, Nerup, J & Pociot, FM 2009, 'Functional SOCS1 polymorphisms are associated with variation in obesity in whites', Diabetes, Obesity and Metabolism, vol. 11, no. 3, pp. 196-203. https://doi.org/10.1111/j.1463-1326.2008.00900.x

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title = "Functional SOCS1 polymorphisms are associated with variation in obesity in whites",

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.",

author = "T Gylvin and J Ek and R. Nols{\o}e and A. Albrechtsen and G Andersen and R. Bergholdt and C Brorsson and Bang-Berthelsen, {C. H.} and T. Hansen and Karlsen, {A. E.} and N Billestrup and K Borch-Johnsen and Torben J{\o}rgensen and Oluf Pedersen and T Mandrup-Poulsen and J. Nerup and Pociot, {Flemming Michael}",

year = "2009",

doi = "10.1111/j.1463-1326.2008.00900.x",

language = "English",

volume = "11",

pages = "196--203",

journal = "Diabetes, Obesity and Metabolism",

issn = "1462-8902",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - Functional SOCS1 polymorphisms are associated with variation in obesity in whites

AU - Gylvin, T

AU - Ek, J

AU - Nolsøe, R.

AU - Albrechtsen, A.

AU - Andersen, G

AU - Bergholdt, R.

AU - Brorsson, C

AU - Bang-Berthelsen, C. H.

AU - Hansen, T.

AU - Karlsen, A. E.

AU - Billestrup, N

AU - Borch-Johnsen, K

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Mandrup-Poulsen, T

AU - Nerup, J.

AU - Pociot, Flemming Michael

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1111/j.1463-1326.2008.00900.x

DO - 10.1111/j.1463-1326.2008.00900.x

M3 - Journal article

C2 - 19215277

SN - 1462-8902

VL - 11

SP - 196

EP - 203

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 3

ER -

Functional SOCS1 polymorphisms are associated with variation in obesity in whites

Abstract

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