The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies

• Published in: Diabetic medicine 2007-10, Vol.24 (10), p.1067-1072
• Main Authors: De Silva, N. M. G., Steele, A., Shields, B., Knight, B., Parnell, K., Weedon, M. N., Hattersley, A. T., Frayling, T. M.
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Biological and medical sciences; Diabetes Mellitus, Type 2 - classification; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - etiology; genetics; Genotype; Humans; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; single nucleotide polymorphism; TCF Transcription Factors - genetics; TCF Transcription Factors - metabolism; Transcription Factor 7-Like 2 Protein; transcription factor 7-like 2; Type 2 diabetes; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2007.02253.x

Aims  Common polymorphisms in the transcription factor 7‐like 2 (TCF7L2) gene are strongly associated with Type 2 diabetes. Many studies include a large proportion of cases enriched for family history or young age of diagnosis and may therefore provide an overestimation of the general population risk. We aimed to compare the impact of TCF7L2 in UK community‐based Type 2 diabetic subjects with that in subjects ascertained for genetic studies. Methods  We genotyped the TCF7L2 polymorphism rs7903146 in 1068 cases from two sources: 487 from 10 GP practices and 601 ascertained for genetic studies, and 2099 control subjects from two sources: 1099 parents from a birth cohort (population control subjects) and 300 subjects with normal fasting glucose aged ≥ 45 years (community control subjects). Results  When compared with Type 2 diabetes cases ascertained for genetic studies, the risk allele frequency in community‐based cases was lower (40 vs. 36%, P = 0.04), but there was no difference in risk allele frequency between community‐based control and population‐based control subjects (31 vs. 30%, P = 0.61). The T allele of rs7903146 increased Type 2 diabetes risk with an odds ratio (OR) of 1.32 (95% CI: 1.13–1.52; P = 0.0002) in community‐based cases, but this OR was lower than the OR of cases enriched for genetic studies [1.58 (95% CI: 1.38–1.80), P = 1.4 × 10−11] and the combined OR of meta‐analysis of 10 studies to date on rs7903146 [1.48 (95% CI: 1.41–1.54), P