Variation of the Transcription Factor 7-Like 2 (TCF7L2) Gene Predicts Impaired Fasting Glucose in Healthy Young Adults
The Cardiovascular Risk in Young Finns Study
- Olli T. Raitakari, MD, PHD1,
- Tapani Rönnemaa, MD, PHD2,
- Risto Huupponen, MD, PHD34,
- Liisa Viikari, MD5,
- Meng Fan, MSC6,
- Jukka Marniemi, MSC7,
- Nina Hutri-Kähönen, MD, PHD8,
- Jorma S.A. Viikari, MD, PHD2 and
- Terho Lehtimäkimd, MD, PHD69
- 1Department of Clinical Physiology, University of Turku, Turku, Finland
- 2Department of Medicine, University of Turku, Turku, Finland
- 3Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
- 4Department of Clinical Pharmacology, Tykslab Health Care District of Southwest Finland, Turku, Finland
- 5Cardiovascular Research Centre, University of Turku, Turku, Finland
- 6University of Tampere Medical School, Tampere, Finland
- 7Department of Health and Functional Capacity, National Public Health Institute, Turku, Finland
- 8Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 9Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
- Address correspondence and reprint requests to Olli T. Raitakari, Department of Clinical Physiology, University of Turku, Kiinamyllynkatu 4-8, FIN-20521 Turku, Finland. E-mail: olli.raitakari{at}utu.fi
- IFG, impaired fasting glucose
- HOMA, homeostasis model assessment
- HOMA-B, HOMA for β-cell function
- HOMA-IR, HOMA for insulin resistance
- SNP, single nucleotide polymorphism
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.
RESEARCH DESIGN AND METHODS
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 …
