AIM: The development of Type 2 diabetes mellitus (T2DM) has been recognized to be associated with a combination of pancreatic beta-cell dysfunction and insulin resistance. Nuclear factor-kappaB (NF-kappaB) has been recognized as one central mediator in the reaction of inflammation and proapoptotic event in beta-cells. A functional polymorphism at the ...

OBJECTIVE: To determine whether the matrix metalloproteinase-9 (MMP-9) c.1562C>T polymorphism has an effect on the plasma MMP-9 levels and the macroangiopathic complications in type 2 diabetes mellitus (T2DM). METHODS: The genotypes and allelic frequencies of the MMP-9 c.1562C>T were examined with polymerase chain reaction and restriction fragment length polymorphism in ...

The majority of type 2 diabetes genome-wide association studies (GWAS) to date have been performed in European-derived populations and have identified few variants that mediate their effect through insulin resistance. The aim of this study was to evaluate two quantitative, directly assessed measures of insulin resistance, namely insulin sensitivity index ...

Myo-inositol oxygenase (MIOX) is the first and rate-limiting enzyme in myo-inositol (MI) metabolism pathway. The increase in MIOX enzyme activity is in proportion to serum glucose concentrations and may be responsible for the MI depletion found in the diabetic complications. The aim was to investigate whether single nucleotide polymorphisms (SNPs) ...

Recent genome-wide association studies have provided an important resource for furthering our understanding of type 2 diabetes mellitus (T2DM) disease mechanisms. Most of these T2DM gene loci affect insulin secretion. We examined the association of rs7903146 variant in the transcription factor 7 like 2 gene (TCF7L2) with T2DM in 333 ...

BACKGROUND: Reduced insulin and insulin-like growth factor-1 (IGF-1) signaling extends the life span of invertebrate and mammals. Recently, reduced insulin receptor substrate-2 (IRS2) signaling was found associated with increased longevity in mice. The aim of our study was to evaluate whether a common polymorphism (Gly1057Asp) in human IRS2 gene is ...

BACKGROUND: The serotonergic system contributes substantially to the regulation of glucose homeostasis and feeding. 5-HTTLPR is a serotonin transporter (5-HTT) gene-linked polymorphic region that regulates the transcriptional activity of 5-HTT. Our aim was to investigate the possible association of 5-HTTLPR polymorphism with type 2 diabetes mellitus and obesity. METHODS: Study ...

BACKGROUND: Insulin growth factor-1 receptor (IGF1R) encodes the insulin-like growth factor 1 receptor, a transmembrane tyrosine kinase receptor located on chromosome 15q26.3, in a region of linkage (LOD = 2.53, P = 0.00032) to Insulin30 on an OGTT in the Old Order Amish. Mouse models with beta-cell-specific deficiency of IGF1R ...

Type-2 diabetes mellitus (T2DM) is a chronic disorder characterized by a varying range of predominant insulin resistance with relative insulin deficiency, to predominant insulin secretory defect with or without insulin resistance. Familial clustering as well as epidemiological studies has shown that genetic factors play a role in the development and ...

INTRODUCTION: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by an early age at onset, autosomal dominant inheritance and a primary defect in the function of the B-cells of the pancreas. We report a family with two members carrying a substitution in both the ...

A one month old baby was admitted for diabetic keto-acidosis. There was no neurological or dysmorphic features. On genetic analysis a heterozygous missense mutation of ABCC8 gene which codes for SUR1 was detected. His insulin requirement progressively came down and by 6 months insulin was stopped and child now maintains ...

In this study we aimed to determine the possible risks for the development of coronary artery disease (CAD) in diabetic (DM(+)) and non-diabetic (DM(-)) patients according to the -374T/A polymorphism of the receptor for advanced glycation end products (RAGE) gene which affects the function of RAGE itself. This study was ...

The study of rare monogenic forms of diabetes and pancreatic B-cell dysfunction provides an unrivalled opportunity to link a specific change in gene function with precise cellular consequences and clinical phenotype in humans. Over the past 20 years there has been considerable success in determining the genetic aetiology of a ...

The association of angiotensin-converting enzyme (ACE) gene polymorphism with diabetic retinopathy (DR) was investigated in many studies with conflicting results. To shed light on these inconclusive findings, a meta-analysis of all available studies relating I (insert)/D (delete) polymorphism to the risk of developing DR was conducted. This meta-analysis included genotype ...

Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and ...

BACKGROUND/AIMS: The role of methylenetetrahydrofolate reductase (MTHFR) and angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for diabetes is still controversial. The aim was to investigate the distribution of ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total homocysteine levels (tHcy) and ACE activity ...

Identification and characterization of the genetic variants underlying type 2 diabetes susceptibility can provide important understanding of the etiology and pathogenesis of type 2 diabetes. We previously identified strong evidence of linkage for type 2 diabetes on chromosome 22 among 3,383 Hypertension Genetic Epidemiology Network (HyperGEN) participants from 1,124 families. ...

AIMS/HYPOTHESIS: LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and ...

AIMS/HYPOTHESIS: The rs1990760 polymorphism (Ala946Thr) of interferon induced with helicase C domain 1 (IFIH1) has been proposed to associate with type 1 diabetes. In this study, association between IFIH1 Ala946Thr and type 1 diabetes was investigated in two distinct white populations, the Hungarians and Finns. METHODS: The rs1990760 polymorphism was ...

BACKGROUND: KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition ...

BACKGROUND: Non-enzymatic glycation is a process, which leads to the formation of advanced glycation endproducts. These compounds are involved in the development of diabetic microvascular complications. Fructosamine-3-kinase (FN3K) is an intracellular enzyme that phosphorylates fructosamines resulting in fructosamine-3-phosphate, which subsequently decomposes to inorganic phosphate, 3-deoxyglucasone and the unmodified amine. Recently, ...

The second isoform of the PPARgamma2 is specific for adipose tissue. In adipocytes, this isoform is involved in the regulation of adipogenesis and lipid storage, insulin and glucose metabolism. Pro12Ala, a missense mutation in exon 2 of PPARG, reduces transcriptional activity of PPARgamma2 and is shown to be associated with ...

OBJECTIVE: Proinflammatory cytokine IL-1beta is capable of decreasing insulin-induced glucose transport. Therefore, we hypothesized that genetic variation in the IL-1 gene family is associated with measures of glucose homeostasis and diabetes. DESIGN AND OUTCOME MEASURES: Fifteen haplotype-tagging single-nucleotide polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes were determined ...

Insulin-degrading enzyme (IDE) is the ubiquitously expressed major enzyme responsible for insulin degradation. Insulin-degrading enzyme gene is located on chromosome region 10q23-q25 and exhibits a well-replicated peak of linkage with type 2 diabetes (T2DM). Several genetic association studies examined IDE gene as a susceptibility gene for T2DM with controversial results. ...

TCF7L2 genetic variants were associated with progression to type 2 diabetes in Europeans. However, the role of TCF7L2 in type 2 diabetes remained uncertain in Chinese. Seventeen tag single nucleotide polymorphisms were genotyped in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family ...

At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered beta-cell function. In this study, we have investigated the combined effects of eight known beta-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps. A total of 447 ...

BACKGROUND: Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. The aim of this study was to investigate the association between the Pro12Ala single nucleotide polymorphism (SNP) at the PPARgamma2 gene and type II diabetes (T2DM) and obesity in an Iranian ...

The IKKbeta/NF-kappaB pathway is known to play an important role in inflammatory response and has also recently been implicated in the process of insulin resistance. We hypothesized that one or more variants in the IkappaBalpha gene (NFKBIA) or surrounding untranslated regions would be associated with insulin sensitivity (S(I)) in Hispanic-American ...

BACKGROUND: ACP1 (acid phosphatase locus 1, a cytosolic low-molecular-weight phosphotyrosin phosphatase) and ADA1 (adenosine deaminase locus 1) are two polymorphic systems involved in immune reactions. Observed interactions at the biochemical and clinical levels between the two systems prompted this investigation of a possible interaction concerning susceptibility to type 1 diabetes. ...

AIM: Vascular endothelial growth factor (VEGF) is important in the pathogenesis of diabetic microvascular complications and the genetic polymorphism of this gene may contribute to the development and progression of diabetic microvascular complications. In this study, we investigated whether a genetic polymorphism of VEGF is associated with diabetic complications. METHODS: ...

Candidate-gene association studies that examined the association between polymorphisms of endothelial nitric oxide synthase (NOS3) gene (G894T, 4b/a, and T786C) and diabetic nephropathy or diabetes leading to severe nephropathy produced inconclusive results. Thus, a meta-analysis of all candidate-gene association studies with endothelial nitric oxide synthase genotyping (7401 cases and 8046 ...

Vitamin D and its analogues are reported to have renoprotective effects in chronic kidney disease including diabetic nephropathy (DN). Vitamin D(3) is converted to 1,25(OH)D(3) by CYP2R1 and CYP27B1. The biological action of 1,25(OH)D(3) is mediated via its receptor. VDR, CYP27B1 or CYP2R1 gene variants could modify the biological activity ...

AIMS: Cardiovascular diseases are the major cause of mortality in patients with diabetes mellitus. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in cardiovascular diseases. The objective of this study was to evaluate the relation between the genotypes of the MCP-1 A-2518G polymorphism and the ...

BACKGROUND AND AIM: Type 2 diabetic patients have an increased prevalence of hypertriglyceridemia. RBP4 has been associated with insulin resistance and hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes. APOA5 is proposed to be a genetic modulator of triglycerides. The aim of this study was to evaluate the ...

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients. Recent genome-wide association studies have identified several genes associated with type 2 diabetes. Here, we examined the association between PTDM and 17 single nucleotide polymorphisms (SNPs) located within 15 genes in a cohort of renal allograft ...

Oxidative stress plays an important role in the development of microangiopathic complications in type 1 diabetes. We investigated polymorphic markers in genes encoding enzymes regulating production of reactive oxygen species in association with diabetic retinopathy or diabetic nephropathy. A total of 124 patients with type 1 diabetes were investigated in ...

Type 2 diabetes mellitus is a complex metabolic disease that is caused by insulin resistance and beta-cell dysfunction. Furthermore, type 2 diabetes has an evident genetic component and represents a polygenic disease. During the last decade, considerable progress was made in the identification of type 2 diabetes risk genes. This ...

Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2 (G6PC2) regulate the glucose-cycling step in pancreatic beta-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships is not well characterized. We tested whether these variants are associated with ...

Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 French individuals. We then selected ...

AIMS/HYPOTHESIS: There has been much focus on the potential role of mitochondria in the aetiology of type 2 diabetes and the metabolic syndrome, and many case-control mitochondrial association studies have been undertaken for these conditions. We tested for a potential association between common mitochondrial variants and a number of quantitative ...

OBJECTIVES: This study was undertaken to investigate the impact of the Pro12Ala (rs1801282) polymorphism of the peroxisome proliferator-activated receptor gamma-2 (PPARgamma-2) gene on obesity or body mass index (BMI) and plasma leptin, insulin, adiponectin and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS: The study included ...

Studies on the association of the Pro12Ala and C1431T polymorphisms of PPAR? with diabetes and obesity have revealed extensive population-dependent variations. However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number ...

Basic fibroblast growth factor (bFGF) is a multifunctional growth factor that may play a significant role in atherosclerotic vascular complications in patients with type 2 diabetes. This study was designed to investigate the association between genetic polymorphisms (-553 T/A, -834 T/A and -921 C/G) in the promoter region of the ...

A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the ...

This study examined the association of insulin resistance with single-nucleotide polymorphism (SNP) 276G>T at adiponectin gene and the plasma long-chain polyunsaturated fatty acids (LCPUFAs) profile in obese children. One hundred thirty-one normolipidaemic obese children aged 8-13 y (53 girls and 68 boys) entered the study. The prevalence of T allele ...

BACKGROUND: Ischemic stroke is a frequent heterogeneous multifactorial disease. A number of genetic mutations and environmental factors have been implicated. A polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases. AIM: A cross-sectional study was performed to ...

The aim of our study was to determine an association between the -174G>C IL-6 polymorphism (rs1800795) and occurrence of retinopathy and nephropathy in type 1 diabetes mellitus (T1DM) patients. Two hundred ten children/adolescents with long-standing T1DM (16.5 +/- 3.8 y; with diabetes duration of 8.4 +/- 3.0 y) were enrolled ...

The insulin-linked polymorphic region (ILPR) is a regulatory sequence in the promoter region upstream of the human insulin gene and is widely recognized as a locus of type 1 diabetes susceptibility. Polymorphism of the ILPR sequence can affect expression of both insulin and the adjacent insulin-like growth factor 2 (IGF-2) ...

Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria. Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo ...

Type 2 diabetes mellitus (T2D) is a main public health problem in the Mexican population. It is characterized by insulin resistance in peripheral tissues and a relative deficiency in the pancreatic beta-cell functions. Diverse single nucleotide polymorphisms (SNPs) of the IRS1 gene have been associated with insulin resistance and T2D ...