Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.
 ...
PMID:Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. 1041 66

Western lifestyle leading to obesity and type 2 diabetes has been associated with increased risk of colorectal cancer (CRC). Diet and related factors may affect the risk by modifying plasma insulin levels. Thus, the inter-individual variation in insulin signaling may play a plausible role in the development of CRC. We hypothesized that functional polymorphisms in the insulin pathway genes INS, INSR, IGFBPI, insulin receptor substrate 1 (IRS1), and IRS2 may be associated with CRC. We studied the association of five single nucleotide polymorphisms (SNPs) with the risk of CRC using a hospital-based case-control design with 712 cases and 748 controls from the Czech Republic. The INSR A-603G promoter SNP, which is located within a known Sp1-binding site, was associated with the risk of CRC, with carriers of the G allele having a decreased risk (odds ratios (OR) 0.71, 95% confidence interval (CI) 0.54-0.93). Carrying the variant allele of the IRS1 Gly972Arg SNP further decreased the risk among the INSR-603G allele carriers (OR 0.28, 95% CI 0.11-0.70). SNPs in the INS, IGFBPI, and IRS2 genes did not affect the risk of CRC. In conclusion, genetic variation in the insulin signaling pathway genes may affect the risk of CRC.
 ...
PMID:Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect. 1791 3

Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARgamma and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.
 ...
PMID:Anthropometry, carbohydrate and lipid metabolism in the East Flanders Prospective Twin Survey: linkage of candidate genes using two sib-pair based variance components analyses. 1882 33

A novel mutation of insulin receptor gene (INSR gene) was identified in a three generation family with phenotypical variety. Proband was a 12-year-old Japanese girl with type A insulin resistance. She showed diabetes mellitus with severe acanthosis nigricans and hyperinsulinemia without obesity. Using direct sequencing, a heterozygous nonsense mutation causing premature termination at amino acid 331 in the alpha subunit of INSR gene (R331X) was identified. Her father, 40 years old, was not obese but showed impaired glucose tolerance. Her paternal grandmother, 66 years old, has been suffered from diabetes mellitus for 15 years. Interestingly, they had the same mutation. One case of leprechaunism bearing homozygous mutation at codon 331 was identified. These findings led to the hypothesis that R331X may contribute to the variation of DM in the general population in Japan. An extensive search was done in 272 participants in a group medical examination that included 92 healthy cases of normoglycemia and 180 cases already diagnosed type 2 DM or detected hyperglycemia. The search, however, failed to detect any R331X mutation in this local population. In addition, the proband showed low level C-peptide/insulin molar ratio, indicating that this ratio is considered to be a useful index for identifying patients with genetic insulin resistance. In conclusion, a nonsense mutation causing premature termination after amino acid 331 in the alpha subunit of the insulin receptor was identified in Japanese diabetes patients. Further investigations are called for to address the molecular mechanism.
 ...
PMID:Phenotypical variety of insulin resistance in a family with a novel mutation of the insulin receptor gene. 2033 96

The Insulin Receptor/PI 3-kinase (INSR/PI3K) signalling pathway is a key regulator of cell and organismal metabolism. Phosphoinositides generated by PI 3-kinases following insulin and other metabolic hormone receptor activation give rise to signalling cascades involving a multitude of effector molecules. The physiological roles of these molecules have been dissected with the use of both pharmacological and genetic tools. Furthermore, tissue-specific mutagenesis has revealed the extent to which individual insulin-target organs and signalling molecules contribute to whole-body carbohydrate and lipid homeostasis. These studies have generated important information with respect to the function of these molecules in normal physiology and their implication in the development of metabolic diseases such as type-2 diabetes and obesity.
 ...
PMID:Phosphoinositide signalling pathways in metabolic regulation. 2051 21

Acanthosis nigricans (AN) is most commonly related to obesity as a manifestation of cutaneous insulin resistance in children and adolescents, while the interaction and time course between AN and obesity and detailed mechanism for the pre- and co-obese appearance of AN (PCOAN) in child are unclear. In this study, the involvement of insulin receptor in child PCOAN was investigated via studying the association of polymorphisms of INSR gene with PCOAN. In total, 99 children with PCOAN and 100 healthy controls recruited were genotyped and analyzed by PCR-RFLP method. Significantly different distributions were found in the frequency of the INSR His1085His genotypes, but not in other INSR genotypes, between the two groups. Our results provide not only the evidence that the T allele of INSR His1085His is correlated with the appearance of PCOAN but revealed that the insulin receptor pathway may play an important role in this PCOAN.
 ...
PMID:The involvement of insulin receptor genotypes in pre- and co-obese acanthosis Nigricans children and adolescent. 2085 34

Type 2 diabetes mellitus (DM) is a common metabolic-endocrine disorder often associated with overweight or obesity. It is a complex disease determined by both predisposing genetic factors and non-genetic environmental factors and interactions between them, leading to impaired beta-cell insulin secretion and peripheral insulin resistance. Insulin resistance is a prominent feature of most patients with type 2 DM and obesity, resulting in a reduced response of target tissues (muscle, liver and fat) to both endogenous and exogenous insulin. There is considerable evidence that heredity is a major contributor to the insulin resistance of type 2 DM. Initially, among those destined to develop diabetes, the beta cells of the pancreas compensate with increased insulin secretion to maintain normal glucose tolerance. Type 2 DM develops when beta cells fail to compensate. Despite of the numerous studies in the recent years, the actual genetic causes of insulin resistance and type 2 DM have not yet been clearly elucidated. Through linkage and "genome-wide" studies, genes were identified most frequently associated with type 2 DM, such as TCF7L2, considered, until recently, the most important gene among those predisposing to type 2 DM. On the other hand, numerous candidate genes have been analyzed for genetic variants that increase susceptibility to type 2 DM. Several variants have been identified in many of these genes, including the insulin receptor gene, INSR, and other genes involved in adipogenesis and beta-cell insulin secretion. In this context, recently our group has identified a new gene involved in the pathogenesis of insulin resistance and type 2 DM: the HMGA1 gene. Functional genetic variants of the HMGA1 gene, capable of reducing the intracellular levels of INSR in insulin target tissues, were found in 10% of patients with type 2 DM in three distinct populations: Italian, North American and French.
 ...
PMID:[Perspectives on the contribution of genetics to the pathogenesis of type 2 diabetes mellitus]. 2225 90

Obesity and diabetes mellitus are associated with low or elevated serum leptin and insulin levels (U-like relation). Mutations in LEP and INS are linked to leptin and insulin decrease while mutations in LEPR and INSR to their increase. Homozygous LEP mutations are associated with the early onset of severe obesity and diverse impairment of physiological functions. Recessive LEPR mutations are associated with similar pathology in homozygous state. Missense mutations of INS are dominant. They induce synthesis of chimeric pro-insulin that may interfere folding and processing of active insulin molecules. In the heterozygous state they cause insulin deficiency and PND. Recessive INS mutations do not induce synthesis of anomalous pro-insulin, and they are associated with PND only in homozygous state. Mutations of INSR induce insulin resistance, lipodystrophy, other pathology, and suggest an important role of insulin in glucose level regulation and in stimulation of fat accumulation as well.
 ...
PMID:[Major gene mutations associated with obesity and diabetes mellitus]. 2370 94

Insulin regulates ovarian phosphatidylinositol-3-kinase (PI3 K) signaling, important for primordial follicle viability and growth activation. This study investigated diet-induced obesity impacts on: (1) insulin receptor (Insr) and insulin receptor substrate 1 (Irs1); (2) PI3K components (Kit ligand (Kitlg), kit (c-Kit), protein kinase B alpha (Akt1) and forkhead transcription factor subfamily 3 (Foxo3a)); (3) xenobiotic biotransformation (microsomal epoxide hydrolase (Ephx1), Cytochrome P450 isoform 2E1 (Cyp2e1), Glutathione S-transferase (Gst) isoforms mu (Gstm) and pi (Gstp)) and (4) microRNA's 184, 205, 103 and 21 gene expression. INSR, GSTM and GSTP protein levels were also measured. Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1, MiR-103, and MiR-21 but increased Kitlg, Akt1, and miR-184 levels relative to lean littermates. These results support that diet-induced obesity potentially impairs ovarian function through aberrant gene expression.
...
PMID:High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression. 2395 4

Colon cancer is the cancer of the large intestine (colon), which is located in the lower part of digestive system. Colon cancer is the third most common cancer in men and the second in women worldwide.Genetic background is thought to play a role in modulating individual risks of this cancer.Many studies support an association between insulin pathway gene polymorphisms and regulation of tumor cell biology in colorectal cancer. This review examines the role of polymorphisms of insulin and obesity pathway genes (IGFs, INS, INSR, ADIPOQ, ADIPOQR, LEP and LEPR) in development of colorectal cancer.
...
PMID:The Association between Polymorphismsin Insulin and Obesity Related Genesand Risk of Colorectal Cancer. 2525 Jan 32


1 2 3 Next >>