Linkage and linkage disequilibrium mapping of genes influencing human obesity in chromosome region 7q22.1-7q35.

Abstract:

:Linkage results suggest that the region of chromosome 7 containing the leptin gene cosegregates with extreme obesity; however, leptin coding region mutations are rare. To investigate whether the leptin flanking sequence and/or a larger 40-cM region (7q22.1-7q35) contributes to obesity, we genotyped individuals from 200 European American families segregating extreme obesity and normal weight (1,020 subjects) using 21 microsatellite markers and two single nucleotide polymorphisms (SNPs) and conducted nonparametric linkage (NPL) analyses. We also carried out transmission disequilibrium tests for 135 European American triads using 27 markers (including eight SNPs). Both quantitative (MERLIN-regress) and qualitative (GENEHUNTER and MERLIN-npl) analyses provided evidence for linkage for BMI (GENEHUNTER NPL = 2.98, 20 cM centromeric to leptin at the marker D7S692; MERLIN Z score = 3.56). Results for several other regions in 7q gave weak linkage. Transmission disequilibrium test (TDT) and quantitative TDT (and quantitative pedigree disequilibrium test) analyses suggest linkage disequilibrium near leptin and other regions of 7q. Our results suggested that there could be two or more genes in chromosome region 7q22.1-7q35 that influence obesity. A new region found by this study (D7S692-D7S523, 7q31.1) has the most consistent linkage results and could harbor obesity-related genes.

journal_name

Diabetes

journal_title

Diabetes

authors

Li WD,Li D,Wang S,Zhang S,Zhao H,Price RA

doi

10.2337/diabetes.52.6.1557

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

1557-61

issue

6

eissn

0012-1797

issn

1939-327X

journal_volume

52

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease.

    abstract::Defects in insulin production and signaling are suspected to share a key role in diabetes and Alzheimer disease (AD), two age-related pathologies. In this study, we investigated the interrelation between AD and diabetes using a high-fat diet (HFD) in a mouse model of genetically induced AD-like neuropathology (3xTg-AD...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-0375

    authors: Vandal M,White PJ,Tremblay C,St-Amour I,Chevrier G,Emond V,Lefrançois D,Virgili J,Planel E,Giguere Y,Marette A,Calon F

    更新日期:2014-12-01 00:00:00

  • Hypoglycemia overrides amylin-mediated regulation of gastric emptying in rats.

    abstract::Amylin, a 37-amino acid peptide hormone co-secreted with insulin, potently governs the rate of gastric emptying. Hypoglycemia, in the absence of agents such as amylin, is reported to accelerate gastric emptying. We asked whether hypoglycemia had a similar action on gastric emptying in the presence of amylin. In prelim...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.47.1.93

    authors: Gedulin BR,Young AA

    更新日期:1998-01-01 00:00:00

  • Insulin binding and response in erythroblastic leukemic cells.

    abstract::Mammalian erythrocytes have been shown to bind, but not to respond to, physiologic doses of insulin. Insulin binding was studied in normal rat erythrocytes and erythroblastic leukemic (EBL) cells by standard 125I-insulin competitive binding assays. EBL cells exhibited marked insulin degradation, which was time, temper...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.7.571

    authors: Galbraith RA,Wise C,Buse MG

    更新日期:1980-07-01 00:00:00

  • Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility.

    abstract::Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistan...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.3.688

    authors: Lan H,Rabaglia ME,Stoehr JP,Nadler ST,Schueler KL,Zou F,Yandell BS,Attie AD

    更新日期:2003-03-01 00:00:00

  • Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe.

    abstract::A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.2337/diabetes.53.12.3193

    authors: Zinman B,Kahn SE,Haffner SM,O'Neill MC,Heise MA,Freed MI,ADOPT Study Group.

    更新日期:2004-12-01 00:00:00

  • Intraislet Ghrelin Signaling Does Not Regulate Insulin Secretion From Adult Mice.

    abstract::Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility of a paracrine mechanism for islet ghrelin to reach high local...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0079

    authors: Gray SM,Niu J,Zhang A,Svendsen B,Campbell JE,D'Alessio DA,Tong J

    更新日期:2019-09-01 00:00:00

  • IGF-1 and leptin associate with fetal HDL cholesterol at birth: examination in offspring of mothers with type 1 diabetes.

    abstract:OBJECTIVE:Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures. RESEARCH DESI...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0585

    authors: Nelson SM,Freeman DJ,Sattar N,Johnstone FD,Lindsay RS

    更新日期:2007-11-01 00:00:00

  • Dual effects of veratridine on glucagon and insulin secretion: dependence upon extracellular and intracellular calcium.

    abstract::The stimulatory effect of the sodium ionophore, veratridine (10, 25 and 50 microM), on glucagon and insulin secretion was investigated using monolayer cultures of newborn rat pancreas. The results suggest that intracellular accumulation of sodium modulates hormone secretion from both alpha- and beta-cells. The action ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.30.5.446

    authors: Kawazu S,Ikeuchi M,Kikuchi M,Kanazawa Y,Fujimoto WY,Kosaka K

    更新日期:1981-05-01 00:00:00

  • Bifunctional properties of peroxisome proliferator-activated receptor gamma1 in KDR gene regulation mediated via interaction with both Sp1 and Sp3.

    abstract::Vascular endothelial growth factor receptor 2 (KDR) plays a critical role in mediating a variety of vasculogenic and angiogenic processes, including diabetic retinopathy. We previously demonstrated that the promoter activity of the KDR gene in retinal capillary endothelial cells (RCECs) was regulated in part by the re...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.5.1222

    authors: Sassa Y,Hata Y,Aiello LP,Taniguchi Y,Kohno K,Ishibashi T

    更新日期:2004-05-01 00:00:00

  • Interleukin-18 promoter polymorphisms in type 1 diabetes.

    abstract::Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.11.3347

    authors: Kretowski A,Mironczuk K,Karpinska A,Bojaryn U,Kinalski M,Puchalski Z,Kinalska I

    更新日期:2002-11-01 00:00:00

  • Improved insulin sensitivity in patients with type I diabetes mellitus after CSII.

    abstract::Tissue sensitivity to insulin was studied using the euglycemic insulin clamp technique (delta plasma insulin above basal 90 microU/ml) in eight patients with type I diabetes mellitus (IDDM) before and after 4-8 mo of continuous subcutaneous insulin infusion (CSII) and in 36 age-matched control subjects. Institution of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.3.s80

    authors: Simonson DC,Tamborlane WV,Sherwin RS,Smith JD,DeFronzo RA

    更新日期:1985-08-01 00:00:00

  • Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell.

    abstract::Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. The Foxo proteins, transcription factors known in other tissues to be negatively regulated by Akt activation, affect proliferation and metabolism. In this st...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-0678

    authors: Martinez SC,Cras-Méneur C,Bernal-Mizrachi E,Permutt MA

    更新日期:2006-06-01 00:00:00

  • Effects of tryptophan on depression and aggression in STZ-D mice.

    abstract::Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.12.1598

    authors: Hilakivi-Clarke LA

    更新日期:1991-12-01 00:00:00

  • The X-linked inhibitor of apoptosis protein enhances survival of murine islet allografts.

    abstract::Allotransplantation of pancreatic islets represents a promising approach to treat type 1 diabetes. Destruction of beta-cells in islet allografts involves multiple immune mechanisms that lead to activation of caspases and apoptotic cell death. The X-linked inhibitor of apoptosis (XIAP) inhibits apoptosis induced by a v...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.9.2533

    authors: Plesner A,Liston P,Tan R,Korneluk RG,Verchere CB

    更新日期:2005-09-01 00:00:00

  • Thermic effect of glucose in obese subjects with non-insulin-dependent diabetes mellitus.

    abstract::A reduced thermic effect of glucose in non-insulin-dependent diabetes mellitus (NIDDM) has been previously reported. To investigate whether this defect is related to 1) a decreased rate of glucose storage, 2) a reduced energy cost of glucose storage, or 3) a defect in the sympathetically mediated component of thermoge...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.36.12.1441

    authors: Ravussin E,Zawadzki JK

    更新日期:1987-12-01 00:00:00

  • Changes in phosphoinositide turnover, Ca2+ mobilization, and protein phosphorylation in platelets from NIDDM patients.

    abstract::Enhanced platelet functions have been demonstrated in patients with non-insulin-dependent diabetes mellitus (NIDDM). This study evaluated abnormalities in platelet signal transduction in diabetic patients, including turnover of phosphoinositides, mobilization of intracellular Ca2+, and phosphorylation of 20,000- and 4...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.39.12.1561

    authors: Ishii H,Umeda F,Hashimoto T,Nawata H

    更新日期:1990-12-01 00:00:00

  • A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.

    abstract::ATP-sensitive potassium (K[ATP]) channels are an essential component of glucose-dependent insulin secretion in pancreatic islet beta-cells. These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family. Mutations in the SUR1 subunit are associated with familial...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.11.1743

    authors: Nestorowicz A,Inagaki N,Gonoi T,Schoor KP,Wilson BA,Glaser B,Landau H,Stanley CA,Thornton PS,Seino S,Permutt MA

    更新日期:1997-11-01 00:00:00

  • Inhibition of Id1 augments insulin secretion and protects against high-fat diet-induced glucose intolerance.

    abstract:OBJECTIVE:The molecular mechanisms responsible for pancreatic β-cell dysfunction in type 2 diabetes remain unresolved. Increased expression of the helix-loop-helix protein Id1 has been found in islets of diabetic mice and in vitro models of β-cell dysfunction. Here, we investigated the role of Id1 in insulin secretion ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0083

    authors: Akerfeldt MC,Laybutt DR

    更新日期:2011-10-01 00:00:00

  • Combinations of nondiabetic parental genomes elicit impaired glucose tolerance in mouse SMXA recombinant inbred strains.

    abstract::Type 2 diabetes in humans is not a single gene disorder but a multifactorial disease caused by the interaction of multiple genes and environmental factors. Recombinant inbred (RI) strains are a powerful tool for analyzing not only single genetic traits but also multifactorial genetic traits. By using the SMXA RI mice,...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.1.180

    authors: Kobayashi M,Ohno T,Tsuji A,Nishimura M,Horio F

    更新日期:2003-01-01 00:00:00

  • Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans.

    abstract::In the fasted rat, efficient glucose-stimulated insulin secretion (GSIS) is absolutely dependent on an elevated level of circulating free fatty acids (FFAs). To determine if this is also true in humans, nonobese volunteers were fasted for 24 h (n = 5) or 48 h (n = 5), after which they received an infusion of either sa...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.10.1613

    authors: Dobbins RL,Chester MW,Daniels MB,McGarry JD,Stein DT

    更新日期:1998-10-01 00:00:00

  • Myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38α MAPK during insulin resistance.

    abstract::Cardiac failure is a major cause of death in patients with type 2 diabetes, but the molecular mechanism that links diabetes to heart failure remains unclear. Insulin resistance is a hallmark of type 2 diabetes, and insulin receptor substrates 1 and 2 (IRS1 and IRS2) are the major insulin-signaling components regulatin...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0095

    authors: Qi Y,Xu Z,Zhu Q,Thomas C,Kumar R,Feng H,Dostal DE,White MF,Baker KM,Guo S

    更新日期:2013-11-01 00:00:00

  • Nuclear protein p8 is associated with glucose-induced pancreatic beta-cell growth.

    abstract::On its own, glucose is a major factor for proliferation of pancreatic beta-cells and is also an essential prerequisite for IGF-I and growth hormone-induced growth of these cells. p8 was originally identified as an emergency gene product upregulated in pancreatic acinar cells in response to acute pancreatitis. p8 was f...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.2007.s82

    authors: Päth G,Opel A,Knoll A,Seufert J

    更新日期:2004-02-01 00:00:00

  • Transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat-fed mice.

    abstract:OBJECTIVE:The catabasis of inflammation is an active process directed by n-3 derived pro-resolving lipid mediators. We aimed to determine whether high-fat (HF) diet-induced n-3 deficiency compromises the resolution capacity of obese mice and thereby contributes to obesity-linked inflammation and insulin resistance. RE...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0054

    authors: White PJ,Arita M,Taguchi R,Kang JX,Marette A

    更新日期:2010-12-01 00:00:00

  • The effect of oxidation on sorbitol pathway kinetics.

    abstract::The rapid conversion of glucose to sorbitol by aldose reductase and the consequent hyperosmolarity of the cytoplasm has been shown to be the primary cause of the so-called "sugar" or "osmotic" cataract in many animal lenses. It is not as clear, however, that hyperosmolarity is the principal factor in the etiology of c...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.4.426

    authors: Barnett PA,González RG,Chylack LT Jr,Cheng HM

    更新日期:1986-04-01 00:00:00

  • T-cell responses to enterovirus antigens in children with type 1 diabetes.

    abstract::Enterovirus infections, implicated in the pathogenesis of type 1 diabetes in a number of studies, may precipitate the symptoms of clinical diabetes and play a role in the initiation of the beta-cell damaging process. The aim of this study was to evaluate whether cellular immune responses to enterovirus antigens are ab...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.8.1308

    authors: Juhela S,Hyöty H,Roivainen M,Härkönen T,Putto-Laurila A,Simell O,Ilonen J

    更新日期:2000-08-01 00:00:00

  • Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.

    abstract::Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.1.6

    authors: Gold G,Pou J,Gishizky ML,Landahl HD,Grodsky GM

    更新日期:1986-01-01 00:00:00

  • Nutrient stress activates inflammation and reduces glucose metabolism by suppressing AMP-activated protein kinase in the heart.

    abstract:OBJECTIVE:Heart failure is a major cause of mortality in diabetes and may be causally associated with altered metabolism. Recent reports indicate a role of inflammation in peripheral insulin resistance, but the impact of inflammation on cardiac metabolism is unknown. We investigated the effects of diet-induced obesity ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-1361

    authors: Ko HJ,Zhang Z,Jung DY,Jun JY,Ma Z,Jones KE,Chan SY,Kim JK

    更新日期:2009-11-01 00:00:00

  • Downregulation of protein kinase C and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes by phorbol esters, glucose, and insulin.

    abstract::Phorbol esters translocatively activate and subsequently downregulate protein kinase C and insulin-stimulated glucose uptake in rat adipocytes. This study examined the possibility that other translocative activators of protein kinase C in rat adipocytes, e.g., insulin and glucose, provoke similar downregulating effect...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.10.1274

    authors: Ishizuka T,Cooper DR,Arnold T,Hernandez H,Farese RV

    更新日期:1991-10-01 00:00:00

  • RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease.

    abstract:OBJECTIVE:Accumulation of glomerular matrix proteins is central to the pathogenesis of diabetic nephropathy, with resident mesangial cells (MCs) known to upregulate matrix protein synthesis in response to high glucose. Because activation of the GTPase RhoA has been implicated in matrix upregulation, we studied its role...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-1149

    authors: Peng F,Wu D,Gao B,Ingram AJ,Zhang B,Chorneyko K,McKenzie R,Krepinsky JC

    更新日期:2008-06-01 00:00:00

  • Streptozotocin-induced diabetes in athymic and conventional BALB/c mice.

    abstract::Spleen cells from conventional BALB/c or athymic mice with streptozotocin (SZ)-induced hyperglycemia failed to raise blood sugar levels when injected into athymic or thymus-sufficient recipients. Passive transfer efforts were unsuccessful despite variations in donor-recipient pairs with respect to age, thymic function...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.2.146

    authors: Beattie G,Lannom R,Lipsick J,Kaplan NO,Osler AG

    更新日期:1980-02-01 00:00:00