The SH2B1 obesity locus and abnormal glucose homeostasis

Lack of evidence for association from a meta-analysis in individuals of European ancestry

S. Prudente, M. Copetti, E. Morini, C. Mendonca, F. Andreozzi, M. Chandalia, R. Baratta, F. Pellegrini, L. Mercuri, D. Bailetti, Nicola Abate, L. Frittitta, G. Sesti, J. C. Florez, A. Doria, V. Trischitta

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background/Aims: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. Methods: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n=47,117) and four other published studies (n=39,448). Results: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR)=0.96; 0.89-1.04) or in the meta-analysis (OR=1.01; 0.98-1.05). Conclusion: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

Original languageEnglish (US)
Pages (from-to)1043-1049
Number of pages7
JournalNutrition, Metabolism and Cardiovascular Diseases
Volume23
Issue number11
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Type 2 Diabetes Mellitus
Meta-Analysis
Homeostasis
Obesity
Glucose
Insulin Resistance
Single Nucleotide Polymorphism
Odds Ratio
Glucose Intolerance
Sequence Deletion
Italy
Genes
Fasting
Body Mass Index
Chromosomes
Genome

Keywords

  • Glucose homeostasis
  • Obesity
  • SH2B1
  • SNP
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

The SH2B1 obesity locus and abnormal glucose homeostasis : Lack of evidence for association from a meta-analysis in individuals of European ancestry. / Prudente, S.; Copetti, M.; Morini, E.; Mendonca, C.; Andreozzi, F.; Chandalia, M.; Baratta, R.; Pellegrini, F.; Mercuri, L.; Bailetti, D.; Abate, Nicola; Frittitta, L.; Sesti, G.; Florez, J. C.; Doria, A.; Trischitta, V.

In: Nutrition, Metabolism and Cardiovascular Diseases, Vol. 23, No. 11, 2013, p. 1043-1049.

Research output: Contribution to journalArticle

Prudente, S, Copetti, M, Morini, E, Mendonca, C, Andreozzi, F, Chandalia, M, Baratta, R, Pellegrini, F, Mercuri, L, Bailetti, D, Abate, N, Frittitta, L, Sesti, G, Florez, JC, Doria, A & Trischitta, V 2013, 'The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry', Nutrition, Metabolism and Cardiovascular Diseases, vol. 23, no. 11, pp. 1043-1049. https://doi.org/10.1016/j.numecd.2013.05.001
Prudente, S. ; Copetti, M. ; Morini, E. ; Mendonca, C. ; Andreozzi, F. ; Chandalia, M. ; Baratta, R. ; Pellegrini, F. ; Mercuri, L. ; Bailetti, D. ; Abate, Nicola ; Frittitta, L. ; Sesti, G. ; Florez, J. C. ; Doria, A. ; Trischitta, V. / The SH2B1 obesity locus and abnormal glucose homeostasis : Lack of evidence for association from a meta-analysis in individuals of European ancestry. In: Nutrition, Metabolism and Cardiovascular Diseases. 2013 ; Vol. 23, No. 11. pp. 1043-1049.
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AU - Copetti, M.

AU - Morini, E.

AU - Mendonca, C.

AU - Andreozzi, F.

AU - Chandalia, M.

AU - Baratta, R.

AU - Pellegrini, F.

AU - Mercuri, L.

AU - Bailetti, D.

AU - Abate, Nicola

AU - Frittitta, L.

AU - Sesti, G.

AU - Florez, J. C.

AU - Doria, A.

AU - Trischitta, V.

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N2 - Background/Aims: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. Methods: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n=47,117) and four other published studies (n=39,448). Results: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR)=0.96; 0.89-1.04) or in the meta-analysis (OR=1.01; 0.98-1.05). Conclusion: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

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