The TCF7L2 locus and type 1 diabetes

<p>Abstract</p> <p>Background</p> <p><it>TCF7L2 </it>belongs to a subfamily of TCF7-like HMG box-containing transcription factors, and maps to human chromosome 10q25.3. A recent study identified genetic association of type 2 diabetes (T2D) with this gene, correlated with diminished insulin secretion. This study aimed to investigate the possibility of genetic association between <it>TCF7L2 </it>and type 1 diabetes (T1D).</p> <p>Methods</p> <p>The SNP most significantly associated with T2D, rs7903146, was genotyped in 886 T1D nuclear family trios with ethnic backgrounds of mixed European descent.</p> <p>Results</p> <p>This study found no T1D association with, and no age-of-onset effect from rs7903146.</p> <p>Conclusion</p> <p>This study suggests that a T2D mechanism mediated by <it>TCF7L2 </it>does not participate in the etiology of T1D.</p

Carcinoma developing in ectopic pancreatic tissue in the stomach: a case report

The development of pancreatic tissue outside the confines of the main gland, without anatomic or vascular connections between them, is a congenital abnormality referred to as heterotopic pancreas. A heterotopic pancreas in the gastrointestinal tract is usually discovered incidentally and the risk of its malignant transformation is extremely low. In this study, we describe the first case of endoepithelial carcinoma arising in a gastric heterotopic pancreas of a 56-year old woman in Greece. She presented with epigastric pain, periodic nausea and vomiting. Esophagogastroduodenoscopy revealed an ulcerated lesion in the gastric antrum, biopsies of which showed intense epithelial dysplasia with incipient malignant degeneration. The pathology report of the distal gastrectomy specimen demonstrated a 2 cm in diameter ulcerative mass in the gastric antrum. Microscopically, an endoepithelial (in situ) carcinoma of the gastric antrum was determined, which in places turned into an microinvasive endomucosal adenocarcinoma. It also incidentally demonstrated heterotopic pancreatic ducts, detected within the mucosa to the muscularis propria of the same region of the stomach, in which an endoepithelial (in situ) carcinoma was evolving. The follow-up course was uneventful 6 months postoperatively

Renal cell cancer without a renal primary

Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and parotid gland metastases in absence of a primary renal source

Association between TCF7L2 gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Transcription factor 7-like 2 (<it>TCF7L2</it>) has been shown to be associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the past two years, but, contradictory results were reported for Chinese and Pima Indian populations. The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the <it>TCF7L2 </it>gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action.</p> <p>Methods</p> <p>Literature-based searching was conducted to collect data and three methods, that is, fixed-effects, random-effects and Bayesian multivariate mete-analysis, were performed to pool the odds ratio (<it>OR</it>). Publication bias and study-between heterogeneity were also examined.</p> <p>Results</p> <p>The studies included 35,843 cases of T2DM and 39,123 controls, using mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian <it>OR </it>for TT homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible interval (<it>CrI</it>): 1.790, 2.157), 1.406 (95% <it>CrI</it>: 1.341, 1.476), respectively, and the population attributable risk (PAR) for the TT/TC genotypes of this variant is 16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG heterozygotes versus GG homozygote was 1.885 (95%<it>CrI</it>: 1.698, 2.088), 1.360 (95% <it>CrI</it>: 1.291, 1.433), respectively. Four <it>OR</it>s among these two polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and the main source of heterogeneity was ethnic differences. Data also showed significant associations between T2DM and the other two polymorphisms, but with low heterogeneity (<it>P </it>> 0.10). Pooled <it>OR</it>s fit a codominant, multiplicative genetic model for all the four polymorphisms of <it>TCF7L2 </it>gene, and this model was also confirmed in different ethnic populations when stratification of IVS3C>T and IVS4G>T polymorphisms except for Africans, where a dominant, additive genetic mode is suggested for IVS3C>T polymorphism.</p> <p>Conclusion</p> <p>This meta-analysis demonstrates that four variants of <it>TCF7L2 </it>gene are all associated with T2DM, and indicates a multiplicative genetic model for all the four polymorphisms, as well as suggests the <it>TCF7L2 </it>gene involved in near 1/5 of all T2MD. Potential gene-gene and gene-environmental interactions by which common variants in the <it>TCF7L2 </it>gene influence the risk of T2MD need further exploration.</p

Social Relationships and Mortality Risk: A Meta-analytic Review

In a meta-analysis, Julianne Holt-Lunstad and colleagues find that individuals' social relationships have as much influence on mortality risk as other well-established risk factors for mortality, such as smoking