Variant of transcription factor 7-like 2 ( TCF7L2 ) gene confers risk of type 2 diabetes

• Published in: Nature genetics Vol. 38; no. 3; pp. 320 - 323
• Main Authors: Grant, Struan F A, Stefansson, Kari, Thorleifsson, Gudmar, Reynisdottir, Inga, Benediktsson, Rafn, Manolescu, Andrei, Sainz, Jesus, Helgason, Agnar, Stefansson, Hreinn, Emilsson, Valur, Helgadottir, Anna, Styrkarsdottir, Unnur, Magnusson, Kristinn P, Walters, G Bragi, Palsdottir, Ebba, Jonsdottir, Thorbjorg, Gudmundsdottir, Thorunn, Gylfason, Arnaldur, Saemundsdottir, Jona, Wilensky, Robert L, Reilly, Muredach P, Rader, Daniel J, Bagger, Yu, Christiansen, Claus, Gudnason, Vilmundur, Sigurdsson, Gunnar, Thorsteinsdottir, Unnur, Gulcher, Jeffrey R, Kong, Augustine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.03.2006
• Subjects: Biological and medical sciences; Blood; Causes of; Chromosome Mapping; Chromosomes, Human, Pair 10; Cohort Studies; Denmark; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA binding proteins; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic aspects; Genetic Carrier Screening; Genetic Predisposition to Disease; Genetic variation; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Health aspects; Humans; Introns; Medical sciences; Microsatellite Repeats; Molecular Sequence Data; Physiological aspects; Population; Reference Values; TCF Transcription Factors - genetics; Transcription Factor 7-Like 2 Protein; Type 2 diabetes; Denmark; Iceland; Endocrinopathy; Type 2 diabetes; Variant; Gene; Metabolic diseases; Risk; Transcription factor
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1732

We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q. We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 × 10−9). This was replicated in a Danish cohort (P = 4.8 × 10−3) and in a US cohort (P = 3.3 × 10−9). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway.