1 Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet
Lack of evidence for association from a meta-analysis in individuals of European ancestry
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.
Nutrition, Metabolism and Cardiovascular Diseases, 2013, Vol 23, Issue 11, p. 1043-9