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Background:Type 2 deiodinase plays a critical role in thyroid hormone homeostasis. A single nucleotide polymorphism in DIO2gene (A/G) in humans has been associated with a ∼20% lower glucose disposal rate and greater insulin resistance in type 2 diabetes (DM2) patients. Objective:This study was designed to test whether homozygosity for the DIO2A/G polymorphism would be associated with risk of DM2 or elevated levels of diabetes intermediate traits. Design and setting:Community-based, longitudinal study. Participants were withdrawn from a subset of unrelated individuals from the Offspring Cohort of the Framingham Heart Study who had DNA collected between 1995 and 1998. Methods:DNA samples from 1633 participants (mean age, 62 years) underwent genotyping of the DIO2A/G polymorphism. Incident DM2 and diabetes-related traits (fasting plasma glucose, mean fasting plasma glucose, 2-hour glucose, hemoglobin A1c, fasting insulin, insulin resistance) were measured. Results:The minor allele (G) frequency was 0.37. Using multivariable regression for intermediate traits and Cox proportional hazards regression for DM2, pvalues were calculated for two models: Model 1: age, age-squared, sex, and smoking; Model 2: Model 1 body mass index. There were no significant associations (all p> 0.20) for any trait examined. For DM2 risk, the hazard ratios associated with A/G or G/G relative to the A/A genotype were 1.0 (95% confidence interval CI 0.7–1.3) and 1.2 (95% CI 0.7–1.9), respectively. Conclusions:Our results indicate that in this community-based sample, there is no association of the DIO2A/G polymorphism with diabetes intermediate trait levels or DM2 risk. [ABSTRACT FROM AUTHOR]