Variation of the Transcription Factor 7-Like 2 (TCF7L2) Gene Predicts Impaired Fasting Glucose in Healthy Young Adults

Abstract

Recently, Grant et al. (1) reported an association between type 2 diabetes and variation in the transcription factor 7-like 2 (TCF7L2) gene. Thereafter, the relation has been replicated in several populations (2–11). The mechanisms by which TCF7L2 variants contribute to the development of type 2 diabetes are incompletely understood. To gain insight on potential mechanisms, we examined the effects of TCF7L2 on the incidence of impaired fasting glucose (IFG) in young adults. The Young Finns Study is a longitudinal study that included 3,596 healthy children and adolescents at baseline in 1980 (12–14). In the present analysis, we used data collected in 1986 and 2001 to assess the effect of the TCF7L2 gene on IFG incidence. Details of methods have been described (15–18). IFG was defined as fasting glucose 5.6–7.0 mmol/l (19,20). Homeostasis model assessment (HOMA) was used to assess β-cell function (HOMA-B) and insulin resistance (HOMA-IR) (21). We genotyped two TCF7L2 single nucleotide polymorphisms (SNPs): 47833C>T (rs7903146) and 98368G>T (rs12255372) (22). These two SNPs were shown to have robust associations with type 2 diabetes and were recommended to be genotyped in attempts at replication (1). Both genotype frequencies were in Hardy-Weinberg equilibrium. Linkage …