Abstract:
:More than 120 published reports have described associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. However, multiple studies of the same variant have often been discordant. From a literature search, we identified previously reported type 2 diabetes-associated SNPs. We initially genotyped 134 SNPs on 786 index case subjects from type 2 diabetes families and 617 control subjects with normal glucose tolerance from Finland and excluded from analysis 20 SNPs in strong linkage disequilibrium (r(2) > 0.8) with another typed SNP. Of the 114 SNPs examined, we followed up the 20 most significant SNPs (P < 0.10) on an additional 384 case subjects and 366 control subjects from a population-based study in Finland. In the combined data, we replicated association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360, PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln. The replication of 12 SNPs of 114 tested was significantly greater than expected by chance under the null hypothesis of no association (P = 0.012). We observed that SNPs from genes that had three or more previous reports of association were significantly more likely to be replicated in our sample (P = 0.03), although we also replicated 4 of 58 SNPs from genes that had only one previous report of association.
journal_name
Diabetesjournal_title
Diabetesauthors
Willer CJ,Bonnycastle LL,Conneely KN,Duren WL,Jackson AU,Scott LJ,Narisu N,Chines PS,Skol A,Stringham HM,Petrie J,Erdos MR,Swift AJ,Enloe ST,Sprau AG,Smith E,Tong M,Doheny KF,Pugh EW,Watanabe RM,Buchanan TA,Valldoi
10.2337/db06-0461subject
Has Abstractpub_date
2007-01-01 00:00:00pages
256-64issue
1eissn
0012-1797issn
1939-327Xpii
56/1/256journal_volume
56pub_type
杂志文章相关文献
DIABETES文献大全abstract::Specific binding of [3H]SCH 23390 to dopamine D1 receptors in the striatum and olfactory tubercle in 14-day alloxan-induced diabetic rats was investigated. The Scatchard analysis revealed decreased D1 receptor density in the striatum (Bmax values were 548 +/- 23 fmol/mg protein for the control and 466 +/- 33 fmol/mg f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.9.1119
更新日期:1992-09-01 00:00:00
abstract::Cardiovascular diseases are the leading cause of morbidity and mortality in diabetes. Lipoprotein lipase (LPL), a major secretory product of macrophages, has been suggested to play a key role in the development of atherosclerosis. In the present study, we evaluated the effect of high glucose on macrophage LPL mRNA exp...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.3.431
更新日期:1998-03-01 00:00:00
abstract:OBJECTIVE:In humans, it is unclear if insulin resistance at the monocyte level is associated with atherosclerosis in vivo. Here we have studied first-degree relatives of patients with type 2 diabetes to investigate whether a reduction in components of the insulin signal transduction pathways, such as the insulin recept...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0162
更新日期:2011-12-01 00:00:00
abstract::NIDDM has a substantial genetic component, but the nature of the genetic susceptibility is largely unknown. Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of NIDDM characterized by an early age of onset and autosomal dominant inheritance, and linkage studies have identified g...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.11.1793
更新日期:1998-11-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) possess immunoregulatory, anti-inflammatory, and proangiogenic properties and, therefore, have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow-derived MSCs have on neonatal porcine islets (NPIs) in vitro and determined islet engraftment an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1068
更新日期:2017-05-01 00:00:00
abstract::Overexpression of hepatocyte growth factor (HGF) in the beta-cell of transgenic mice enhances beta-cell proliferation, survival, and function. In the current studies, we have used conditional ablation of the c-met gene to uncover the physiological role of HGF in beta-cell growth and function. Mice in which c-met is in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.7.2090
更新日期:2005-07-01 00:00:00
abstract::Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL ar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0811
更新日期:2020-05-01 00:00:00
abstract::Exercise-induced hyperinsulinism (EIHI) is an autosomal dominant disorder characterized by inappropriate insulin secretion in response to vigorous physical exercise or pyruvate injection. Activating mutations in the monocarboxylate transporter-1 (MCT1, SLC16A1) promoter have been linked to EIHI. Expression of this pyr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1531
更新日期:2012-07-01 00:00:00
abstract::To examine the mechanism of the arginine-induced rise in blood glucose concentration, splanchnic glucose output (SGO) and precursor uptake were studied during i.v. infusion of arginine (30 g/30 min) with and without somatostatin infusion (500 microgram/h, 90 min) in postabsorptive and in 60-h fasted healthy subjects. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.2.126
更新日期:1979-02-01 00:00:00
abstract::Dynamic aspects of whole body alanine and glycine metabolism have been explored in insulin-dependent (type I) diabetic subjects. Using a primed, continuous intravenous (i.v.) infusion of [2H3]alanine and [15N]glycine given simultaneously with [1-13C]leucine, whole body alanine and glycine fluxes and their rates of de ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.1.67
更新日期:1985-01-01 00:00:00
abstract::To treat insulin lipoatrophy, small amounts of dexamethasone (4 micrograms/unit) were added to insulin injections in nine patients. Six cases showed significant improvement of dexamethasone-treated sites over that of control sites in six months. With the continued use of dexamethasone-containing insulin, they remained...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.4.296
更新日期:1977-04-01 00:00:00
abstract::Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0387
更新日期:2016-09-01 00:00:00
abstract::Thiazolidinediones and exercise are both known to improve insulin action independently. Therefore, we determined whether combined therapy could normalize insulin action in the Zucker fatty (ZF) rat. Rats were fed troglitazone as a 0.2% food admixture over a 3-week exercise training period (treadmill running 5 days/wee...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.12.2154
更新日期:2000-12-01 00:00:00
abstract::Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1320
更新日期:1989-10-01 00:00:00
abstract::The allelic forms of the human leukocyte antigen (HLA)-DQ beta-chain (DQB1) have been recognized as the best markers of insulin-dependent diabetes mellitus (IDDM) susceptibility. We describe a method that allows the recognition of these DQB1 alleles without the use of either allele-specific oligonucleotide probes or r...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.12.1617
更新日期:1989-12-01 00:00:00
abstract::We report a genomewide linkage analysis of a large consanguineous family segregating autosomal recessively inherited neonatal diabetes and the identification of a novel neonatal diabetes locus. Neonatal diabetes was characterized by low levels of circulating C-peptide with very low to undetectable levels of insulin in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.10.2636
更新日期:2003-10-01 00:00:00
abstract:OBJECTIVE:To characterize normal and malformed embryos within the same litters from control and diabetic rats for expression of genes related to metabolism of reactive oxygen species (ROS) or glucose as well as developmental genes. RESEARCH DESIGN AND METHODS:Embryos from nondiabetic and streptozotocin-induced diabeti...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0830
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVE:IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3'-UTR of IKZF1 with C-ALL susceptibility, we tested...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0446
更新日期:2011-03-01 00:00:00
abstract::Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restrict...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1326
更新日期:2003-06-01 00:00:00
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
更新日期:2005-09-01 00:00:00
abstract::The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db18-0682
更新日期:2019-02-01 00:00:00
abstract:OBJECTIVE:In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. In contrast, aberrantly high levels of triglycerides in the blood ("hypertriglyceridemia") represent a hallmark of the metabolic syndrome and type 2 diabetes. As hypertriglyceri...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1184
更新日期:2009-05-01 00:00:00
abstract::Obesity is associated with an increase in the fractional contribution of gluconeogenesis (GNG) to glucose production. We tested if this was related to the altered protein metabolism in obesity. GNG(PEP) (via phosphoenol pyruvate [PEP]) was measured after a 17-h fast using the deuterated water method and 2H nuclear mag...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.03.06.db05-1117
更新日期:2006-03-01 00:00:00
abstract::An A-to-G transition in the mitochondrial tRNALeu(UUR) gene at base pair 3243 has been shown to be associated with the maternally transmitted clinical phenotype of NIDDM and sensorineural hearing loss in white and Japanese pedigrees. We have detected this mutation in 25 of 50 tested members of five white French pedigr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.4.478
更新日期:1996-04-01 00:00:00
abstract::The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributi...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db16-0152
更新日期:2016-06-01 00:00:00
abstract::Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0630
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVE:Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms by which this gene affects type 2 diabetes risk. RESEARCH DESIGN AND METHODS:Eight subjects with risk-conferring TCF7L2 genotypes (TT o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1169
更新日期:2010-02-01 00:00:00
abstract::Estrogen-related receptor γ (ERRγ) is a major positive regulator of hepatic gluconeogenesis. Its transcriptional activity is suppressed by phosphorylation signaled by insulin in the fed state, but whether posttranslational modification alters its gluconeogenic activity in the fasted state is not known. Metabolically a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1523
更新日期:2016-10-01 00:00:00
abstract::Nearly 20 years ago, it was suggested that individuals exist who are not obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes, hypertriglyceridemia, and premature coronary heart disease. Since then it has become in...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.47.5.699
更新日期:1998-05-01 00:00:00
abstract::The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a cl...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0287
更新日期:2019-10-01 00:00:00