Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0497406 (overweight)
 26,365 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1alpha (HNF1alpha) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1alpha-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1alpha germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating beta-catenin mutation was found in 10% of HCA. These beta-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress beta-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express beta-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1alpha-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.
 ...
PMID:Hepatocellular adenoma: what is new in 2008. 1966 72

Genetic studies have identified a glutamate-ammonia ligase gene (GLUL) polymorphism associated with cardiovascular disease morbidity and mortality among people with type 2 diabetes (T2D). We sought to determine whether GLUL rs10911021 is associated prospectively with adjudicated cardiovascular composite end points among overweight/obese individuals with T2D and whether a lifestyle intervention resulting in weight loss could diminish this association. Look AHEAD is a randomized, controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Look AHEAD participants included in this report were 3,845 overweight/obese individuals with T2D who provided consent for genetic analyses. Over a median of 9.6 years of follow-up, the risk (C) allele for GLUL rs10911021 was significantly associated with the primary composite end point of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina among individuals with no history of cardiovascular disease (CVD) at baseline using additive genetic models (hazard ratio 1.17 [95% CI 1.01-1.36]; P = 0.032). Results appeared more consistent in recessive models and among individuals with no known history of CVD at baseline; ILI did not alter these associations. These results extend the association of GLUL rs10911021 to incident CVD morbidity and mortality in the setting of T2D.
 ...
PMID:Prospective Association of GLUL rs10911021 With Cardiovascular Morbidity and Mortality Among Individuals With Type 2 Diabetes: The Look AHEAD Study. 2755 79