Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Context-Specific Risk of Type 2 Diabetes in African American and Caucasian Adults: The Atherosclerosis Risk in Communities Study

OBJECTIVE—Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with type 2 diabetes, large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on type 2 diabetes in the context of metabolic risk factors of type 2 diabetes. RESEARCH DESIGN AND METHODS—We investigated the association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes in 2,727 African American and 9,302 Caucasian participants without diabetes who were inducted into the Atherosclerosis Risk in Communities study in 1987–1989 and followed for 9 years. RESULTS—A total of 485 and 923 cases of type 2 diabetes were identified in African Americans and Caucasians, respectively. Compared with homozygous CC individuals, heterozygous CT and homozygous TT individuals had higher cumulative incidence of type 2 diabetes over 9 years of follow-up: 11.3% (95% CI 10.2–12.4) vs. 21.1% (20.8–21.4) and 27.9% (19.3–36.5) in African Americans, respectively, and 9.7% (8.8–10.6) vs. 11.3% (10.2–12.4) and 13.6% (11.1–16.1), respectively, in Caucasians. Individuals with the risk allele had the highest hazards of diabetes if they were obese and had low HDL cholesterol, followed by individuals with any one and none of the traits. CONCLUSIONS—Our study provides the first significant evidence of association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes risk in a large African American population and also demonstrates that the diabetes risk conveyed by the rs7903146 risk allele is substantially increased in the context of some metabolic risk factors for type 2 diabetes. Our study findings need to be replicated in other large, population-based studies.