A common polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 transcription start site has been associated with obesity in Caucasian and African-American populations, with the hypothesis that an alteration in gene expression results in elevated plasma triglyceride levels. The goal of this study was to verify the findings in a cohort of 2721 healthy Caucasian men (second Northwick Park Heart Study), and a separate study of 747 type 2 diabetic patients from Caucasian, Afro-Caribbean and Indian groups (University College London Diabetes and Cardiovascular Disease Study). The rs7566605 single-nucleotide polymorphism (SNP) was not related to plasma triglyceride levels in either study, and we found no association with body mass index or obesity in either cohort, despite having the power to detect the previously reported effect. This suggests that, at the least, the true size of the effect on obesity of this SNP is likely to be considerably less than reported previously.