Association of uncoupling protein-2 -866G/A and Ala55Val polymorphisms with susceptibility to type 2 diabetes mellitus

Abstract Objective: Uncoupling protein 2 (UCP2) plays a crucial role in energy homeostasis via regulation of insulin secretion, free fatty acid concentrations, and lipid metabolism. This study aimed to investigate the association of 45-bp ins/del polymorphism of UCP2 with susceptibility to NAFLD (Non Alcoholic Fatty Liver Disease) and T2DM (Type 2 Diabetes Mellitus). DNA was extracted from the white blood cells of the subjects, and the gene polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In this study, 72 patients with NAFLD, 71 healthy individuals as control, 80 patients with T2DM, and 77 healthy controls were enrolled in the study.Results: A higher prevalence of insertion/insertion genotype was observed in T2DM patients compared to the controls (p- value˂ 0.05). But, there was no difference in genotype distribution between NAFLD patients and controls (p-value> 0.05). NAFLD patients with D/D, D/I genotype had higher triglyceride, ALT, and AST levels; however, their HDL levels were lower than healthy controls. Patients with T2DM with D/D or D/I genotype also had significantly higher fasting serum glucose (FSG). While we found an association between the 45bp I/D polymorphism in 3ʹUTR of UCP2 and T2DM, no any correlation between this polymorphism and NAFLD was identified.

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Increased Plasma Manganese, Partially Reduced Ascorbate,1 and Absence of Mitochondrial Oxidative Stress in Type 2 Diabetes Mellitus: Implications for the Superoxide Uncoupling Protein 2 (Ucp-2) Pathway

Biological Trace Element Research ◽

10.1007/s12011-007-0069-x ◽

2007 ◽

Vol 120 (1-3) ◽

pp. 19-27 ◽

Cited By ~ 7

Author(s):

J. I. Anetor ◽

O. A. Asiribo ◽

K. S. Adedapo ◽

T. S. Akingbola ◽

O. S. Olorunnisola ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Mitochondrial Oxidative Stress

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The role of uncoupling protein 2 (UCP2) on the development of type 2 diabetes mellitus and its chronic complications

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302011000400001 ◽

2011 ◽

Vol 55 (4) ◽

pp. 239-248 ◽

Cited By ~ 55

Author(s):

Bianca Marmontel de Souza ◽

Taís Silveira Assmann ◽

Lúcia Maria Kliemann ◽

Jorge Luiz Gross ◽

Luís Henrique Canani ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Acid Metabolism ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Chronic Complications ◽

Ucp2 Gene

It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (DM2) and its chronic complications, and that genetically susceptible subjects can develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2. Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism. All these mechanisms are associated with DM2 pathogenesis and its chronic complications. Therefore, UCP2 is a candidate gene for the development of these disorders. Indeed, several studies have reported that three common polymorphisms in UCP2 gene are possibly associated with DM2 and/or obesity. Only a few studies investigated these polymorphisms in relation to chronic complications of diabetes, with inconclusive results.

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Analysis of Uncoupling Protein 1 and β3-adrenergic Receptor Single Nucleotide Polymorphisms in Saudi Population with Type 2 Diabetes Mellitus

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4886 ◽

2020 ◽

Vol 8 (A) ◽

pp. 699-705

Author(s):

Fathy М. Elfasakhany ◽

Abdulah M. Karawagh ◽

Shahid S. Siddiqui ◽

Magdi A. Eldamarawi

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphism ◽

Adrenergic Receptor ◽

Uncoupling Protein ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

The Relationship

BACKGROUND: Uncoupling proteins (UCP) and β3-adrenergic receptor (ADRB3) gene polymorphism have been implicated in the susceptibility to type 2 diabetes mellitus (T2DM) but the results are inconsistent and inconclusive. AIM: The aim was to investigate the relationship between -3826A/G (rs1800592) of UCP 1 and ADRB3 Trp64Arg (C/T) (rs4994) gene polymorphism and the incidence of T2DM among Saudis. METHODS: Genotyping of both UCP1 and ADRB3 genes was carried out in 110 healthy controls and 108 unrelated Saudis with T2DM using polymerase chain reaction-based restriction fragment length polymorphism. RESULTS: The genotype and allele frequencies of the UCP1 gene did not differ significantly between diabetic subjects and controls (p > 0.05). However, the CT genotype and the T allele of ADRB3 were higher in diabetic subjects compared with the controls while the CC genotype and C allele were higher in the controls relative to the diabetic subjects (Odds ratios [OR]: 7.85, 95% confidence interval [CI]: 4.23–14.59, p < 0.001 and OR: 7.434 95% CI: 4.026–13.39, p < 0.001, respectively). CONCLUSION: The UCP1 -3826A/G polymorphism may not be associated with the susceptibility to T2DM among Saudis while T allele of ADRB3 may be related to the risk of T2DM, whereas the CC genotype and C allele may confer protection to T2DM.

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The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302012000400001 ◽

2012 ◽

Vol 56 (4) ◽

pp. 215-225 ◽

Cited By ~ 56

Author(s):

Letícia de Almeida Brondani ◽

Taís Silveira Assmann ◽

Guilherme Coutinho Kullmann Duarte ◽

Jorge Luiz Gross ◽

Luís Henrique Canani ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Metabolic Diseases ◽

Uncoupling Protein ◽

Uncoupling Protein 1 ◽

Exon 2 ◽

Brown Adipose

It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

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