The type 2 deiodinase (DIO2) A/G polymorphism is not associated with glycemic traits: the Framingham Heart Study

Type 2 deiodinase plays a critical role in thyroid hormone homeostasis. A single nucleotide polymorphism in DIO2 gene (A/G) in humans has been associated with a approximately 20% lower glucose disposal rate and greater insulin resistance in type 2 diabetes (DM2) patients.

This study was designed to test whether homozygosity for the DIO2 A/G polymorphism would be associated with risk of DM2 or elevated levels of diabetes intermediate traits.

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 Participants were withdrawn from a subset of unrelated individuals from the Offspring Cohort of the Framingham Heart Study who had DNA collected between 1995 and 1998.

DNA samples from 1633 participants (mean age, 62 years) underwent genotyping of the DIO2 A/G polymorphism. Incident DM2 and diabetes-related traits (fasting plasma glucose, mean fasting plasma glucose, 2-hour glucose, hemoglobin A(1c), fasting insulin, insulin resistance) were measured.

The minor allele (G) frequency was 0.37. Using multivariable regression for intermediate traits and Cox proportional hazards regression for DM2, p values 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.

Our results indicate that in this community-based sample, there is no association of the DIO2 A/G polymorphism with diabetes intermediate trait levels or DM2 risk.