Variant of Transcription Factor 7-Like 2 (TCF7L2) Gene and the Risk of Type 2 Diabetes in Large Cohorts of U.S. Women and Men
- Cuilin Zhang1,
- Lu Qi1,
- David J. Hunter1,2,3,
- James B. Meigs4,
- JoAnn E. Manson2,3,5,
- Rob M. van Dam1 and
- Frank B. Hu1,2,3
- 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- 2Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- 3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
- 4General Internal Medicine and Clinical Epidemiology Units, General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- 5Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- Address correspondence and reprint requests to Cuilin Zhang MD, PhD, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. E-mail: or
Emerging evidence indicates that variation in the transcription factor 7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2 diabetes. In a prospective, nested, case-control study (n = 3,520) within the Nurses’ Health Study (687 type 2 diabetic case and 1,051 control subjects) and the Health Professionals Follow-up Study (886 case and 896 control subjects), we examined the association of a common variant of the TCF7L2 gene (rs12255372 [T/G]) with type 2 diabetes risk among Caucasians. Frequencies of the T-allele were significantly higher among case than control subjects; each copy of the T-allele was associated with a 1.32-fold (P = 0.0002) and 1.53-fold (P < 0.0001) increased type 2 diabetes risk in women and men, respectively. The odds ratios (95% CI) associated with homozygous carriers of the T-allele were 1.86 (1.30–2.67) and 2.15 (1.48–3.13) in women and men, respectively. Population-attributable risks for diabetes associated with the T-allele were 14.8 and 22.3% for women and men, respectively. In a meta-analysis of 3,347 case and 3,947 control sujects, each copy of the T-allele was associated with a 1.48-fold increased risk (P < 10−16). Our findings confirm that the TCF7L2 gene represents an important locus for predicting inherited susceptibility to type 2 diabetes.
- GLP-1, glucagon-like peptide 1
- HPFS, Health Professionals Follow-up Study
- LD, linkage disequilibrium
- NHS, Nurses’ Health Study
- SNP, single nucleotide polymorphism
- TCF-4, transcription factor 4
- Received May 10, 2006.
- Accepted June 13, 2006.