Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of impaired fasting glucose in African American and Caucasian adults: The atherosclerosis risk in communities (ARIC) study

Background: Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with impaired fasting glucose (IFG) in Caucasians, data from large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on IFG in the context of metabolic risk factors for diabetes. Methods: We investigated the association between the TCF7L2 rs7903146 polymorphism and incident IFG defined as fasting serum glucose levels of 100-125 mg/dL (5.6-6.9 mmol/L) in 1377 African American and 5152 Caucasian participants without diabetes and IFG at intake who participated in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 to1989 and were followed for 9 years. Results: Incident IFG was identified in 810 (58.8%) African American and 2652 (51.5%) Caucasian participants. Compared to homozygous CC Caucasian individuals, heterozygous CT [hazard ratio (HR) = 1.09 (95% CI = 1.03-1.15)] and homozygous TT [1.18 (1.05-1.33)] individuals had significantly higher risk of developing IFG over 9-year follow-up. The association between rs7903146 and IFG risk was stronger in Caucasians with obesity [HR_{CT vs. CC} = 1.28 (1.12, 1.47); HR _{TT vs. CC} = 1.65 (1.25, 2.17)] or high triglycerides [HR _{CT vs. CC} = 1.31(1.10, 1.56); HR_{TT vs. CC} = 1.72 (1.21, 2.43)]. No association of the TCF7L2 rs7903146 polymorphism and incident IFG was noted in African Americans. Conclusions: Our study replicates the association between rs7903146 and IFG risk in a population-based, longitudinal cohort of Caucasians but not in African Americans. For the first time, our study provides evidence for interactions between TCF7L2 and metabolic risk factors on the occurrence of IFG in Caucasians.