{
  "titles": [
    "2010 - Candidate Gene and Genome-Wide Association Studies in Behavioral Medicine.pdf",
    "2009 - Pathomechanisms of Type 2 Diabetes Genes.pdf",
    "2014  - Dorothy Hodgkin Lecture 2014 Understanding genes identified by genome\u2010wide association.pdf",
    "2015 - Type 2 Diabetes Mellitus and the Association of Candidate Genes.pdf",
    "2012 - Type 2 Diabetes Genetics Beyond GWAS.pdf",
    "2015 - Diabetes mellitus The epidemic of the century.pdf",
    "2013 - TCF7L2 gene polymorphisms and type 2 diabetes association with diabetic retinopathy and cardiovascular autonomic neuropathy.pdf",
    "2007 - A German genome-wide linkage scan for type 2 diabetes supports the existence of a metabolic syndrome locus on chromosome 1p36.13 and a type 2 diabetes locus on chromosome 16p12.pdf",
    "2015 - Diabetes mellitus The epidemic of the century.pdf",
    "2013 - TCF7L2 gene polymorphisms and type 2 diabetes association with diabetic retinopathy and cardiovascular autonomic neuropathy.pdf"
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    "T. I., de Bakker, P . I. et al (2006). TCF7L2",
    "single nucleotide polymorphisms in TCF7L2 are reproduc-ibly associated with type 2 diabetes and reduce the insulinresponse to glucose in nondiabetic individuals. Diabetes55:28902895 135. Cauchi S, Meyre D, Dina C, Choquet H, Samson C, Gallina S, Balkau B, Charpentier G, Pattou F, StetsyukV, Scharfmann R, Staels B, Fru  hbeck G, Froguel P 2006 Transcription factor TCF7L2 genetic study in the Frenchpopulation: expression in human /H9252-cells and adipose tissue",
    "rs7903146 and rs12255372 in intron 3 of the TCF7L2 gene [20], associated with a ~45% increase in Type 2 diabetes risk per allele. As such, the TCF7L2 locus presently repre- sents the strongest known genetic determinant of Type 2diabetes. Risk allele carriers show impaired insulin produc-tion [21] and b-cell dysfunction in vitro [22]. TCF7L2 (previously referred to as TCF-4) is a high-mobility group box-containing transcription factor involved in Wingless-type MMTV integration site (Wnt)",
    "et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2  diabetes. Nat Genet . 2006;38:320-23.   Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome- [9] wide association study identifies novel risk loci for type 2 diabetes. Nature .  2007;445:881-85.  Kirchhoff K, Machicao F, Haupt A, Schafer SA, Tschritter O, Staiger H, et al. [10] Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated",
    "transcription factor 7-like 2 ( TCF7L2 ) gene confers risk of type 2 diabetes. Nat Genet. 2006; 38:320323. [PubMed: 16415884] 172. Gloyn AL, Noordam K, Willemsen MA, Ellard S, Lam WW, et al. Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Diabetes. 2003; 52:24332440. [PubMed: 12941786] 173. Pearson ER, Donnelly LA, Kimber C, Whitley A, Doney AS, et al. Variation in TCF7L2",
    "L. Mechanisms by which common variants in the TCF7L2 gene  increase risk of type 2 diabetes. J Clin Invest  2007; 117: 2155-2163  [PMID: 17671651 DOI: 10.1172/JCI30706] 164 Gloyn AL , Braun M, Rorsman P. Type 2 diabetes susceptibility  gene TCF7L2 and its role in beta-cell function. Diabetes  2009; 58:  800-802 [PMID: 19336690 DOI: 10.2337/db09-0099] 165 da Silva Xavier G , Loder MK, McDonald A, Tarasov AI, Carzaniga  R, Kronenberger K, Barg S, Rutter GA. TCF7L2 regulates late",
    "tion. Although the disease progression results from aninterplay of environmental factors and genetic predisposi- tion, in recent years TCF7L2 gene has been considered the strongest genetic determinant for the risk of developingT2DM [ 24,19,20]. The gene encodes a transcription factor of the canonical Wnt signaling pathway, expressed in several tissues, known to have developmental roles indetermining cell fate, survival, proliferation and movement [9]. Wnt signaling plays an important role also in B-cell",
    "transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2diabetes. Nat Genet 38:320 3231422 Diabetologia (2007) 50:1418 1422",
    "genes which also play a significant role in the risk and  pathogenesis of the disease[158,159]. The association  of TCF7L2  gene variants with type 2 diabetes and  its mechanism of action received special attention  by several investigators[161,162]. Over expression of the protein was shown to decrease the sensitivity of  beta islet cells to secrete insulin[163,164] and was more  precisely involved in the regulation of secretary granule  fusion that constitute a late event in insulin secretion",
    "Muggeo M, Stoico V, Negri C, Pignatti PF, Bonora E, Bonadonna RC (2011) Variants and haplotypes of TCF7L2 are associatedwithb-cell function in patients with newly diagnosed type 2 diabetes: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 1. J Clin Endocrinol Metab 96(2):E389E393 13. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ, National Heart, Lung, and Blood Institute, American College of Cardiol-"
  ],
  "answer": "The gene TCF7L2 is primarily involved in Type 2 diabetes. This association is well-documented across multiple sources:  1. Single nucleotide polymorphisms in TCF7L2 are reproducibly associated with Type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals [2]. 2. The TCF7L2 locus represents the strongest known genetic determinant of Type 2 diabetes, with risk allele carriers showing impaired insulin production and beta-cell dysfunction [3]. 3. Variants of the TCF7L2 gene confer risk of Type 2 diabetes [4], [5]. 4. TCF7L2 is considered the strongest genetic determinant for the risk of developing Type 2 diabetes [7]. 5. Overexpression of TCF7L2 protein decreases the sensitivity of beta islet cells to secrete insulin, which is involved in the regulation of insulin secretion [9].  Thus, the gene TCF7L2 is significantly involved in Type 2 diabetes.",
  "question": "In which diseases is the gene TCF7L2 involved?"
}