The  UCP2 -866G/A, Ala55Val and UCP3 -55C/T 
polymorphisms are associated with premature coronary artery disease and
cardiovascular risk factors in Mexican population

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Abstract

We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val ( C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 - 55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V ( C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) ( Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) ( Pc = 0.001) and high VAT/SAT ratio ( Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF ( Pc = 0.003), low levels of SAF ( Pc = 0.001) and a high VAT/SAT ratio ( Pc = 0.002), whereas patients with the UCP3 -55 (rs1800849) TT presented high levels of VAF ( Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors.

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Most cited references 58

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Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.

C Fleury, M Neverova, S. Collins … (1997)

A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.

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Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.

Anna Norhammar, Ake Tenerz, Göran Nilsson … (2002)

Glycometabolic state at hospital admission is an important risk marker for long-term mortality in patients with acute myocardial infarction, whether or not they have known diabetes mellitus. Our aim was to ascertain the prevalence of impaired glucose metabolism in patients without diagnosed diabetes but with myocardial infarction, and to assess whether such abnormalities can be identified in the early course of a myocardial infarction. We did a prospective study, in which we enrolled 181 consecutive patients admitted to the coronary care units of two hospitals in Sweden with acute myocardial infarction, no diagnosis of diabetes, and a blood glucose concentration of less than 11.1 mmol/L. We recorded glucose concentrations during the hospital stay, and did standardised oral glucose tolerance tests with 75 g of glucose at discharge and again 3 months later. The mean age of our cohort was 63.5 years (SD 9) and the mean blood glucose concentration at admission was 6.5 mmol/L (1.4). The mean 2-h postload blood glucose concentration was 9.2 mmol/L (2.9) at hospital discharge, and 9.0 mmol/L (3.0) 3 months later. 58 of 164 (35%, 95% CI 28-43) and 58 of 144 (40%, 32-48) individuals had impaired glucose tolerance at discharge and after 3 months, respectively, and 51 of 164 (31%, 24-38) and 36 of 144 (25%, 18-32) had previously undiagnosed diabetes mellitus. Independent predictors of abnormal glucose tolerance at 3 months were concentrations of HbA(1c) at admission (p=0.024) and fasting blood glucose concentrations on day 4 (p=0.044). Previously undiagnosed diabetes and impaired glucose tolerance are common in patients with an acute myocardial infarction. These abnormalities can be detected early in the postinfarction period. Our results suggest that fasting and postchallenge hyperglycaemia in the early phase of an acute myocardial infarction could be used as early markers of high-risk individuals.

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Health consequences of obesity in the elderly: a review of four unresolved questions.

M. Zamboni, E. Zoico, J. Meigs … (2005)

Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity.

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Author and article information

Journal

Journal ID (nlm-ta): Genet Mol Biol

Journal ID (iso-abbrev): Genet. Mol. Biol

Journal ID (publisher-id): gmb

Title: Genetics and Molecular Biology

Publisher: Sociedade Brasileira de Genética

ISSN (Print): 1415-4757

ISSN (Electronic): 1678-4685

Publication date (Electronic): 21 May 2018

Publication date (Print): Apr-Jun 2018

Volume: 41

Issue: 2

Pages: 371-378

Affiliations

[1 ] normalizedInstituto Nacional de Cardiología orgnameInstituto Nacional de Cardiología orgdiv1Department of Physiology Mexico D.F. Mexico originalDepartment of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico D.F., Mexico

[2 ] normalizedInstituto Nacional de Cardiología orgnameInstituto Nacional de Cardiología orgdiv1Department of Endocrinology Mexico D.F. Mexico originalDepartment of Endocrinology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico D.F., Mexico

[3 ] normalizedInstituto Nacional de Cardiología orgnameInstituto Nacional de Cardiología orgdiv1Department of Molecular Biology Mexico D.F. Mexico originalDepartment of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico D.F., Mexico

[4 ] normalizedInstituto Nacional de Cardiología orgnameInstituto Nacional de Cardiología orgdiv1Department of Immunology Mexico D.F. Mexico originalDepartment of Immunology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico D.F., Mexico

Author notes

Send correspondence to Gilberto Vargas-Alarcón, Instituto Nacional de Cardiología “Ignacio Chávez” Juan Badiano No 1, Col. Sección XVI, 14080 Mexico, D.F., Mexico.E-mail: gvargas63@ 123456yahoo.com .

Article

DOI: 10.1590/1678-4685-GMB-2017-0008

PMC ID: 6082227

PubMed ID: 29786102

SO-VID: dd0e5ce0-55c9-4422-b638-3e30f0dbda44

License:

License information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (type CC-BY), which permits unrestricted use, distribution and reproduction in any medium, provided the original article is properly cited.

History

Date received : 10 January 2017

Date accepted : 18 October 2017

Page count

Figures: 0, Tables: 5, Equations: 0, References: 49, Pages: 8

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The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population

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Most cited references 58

Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.

Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.

Health consequences of obesity in the elderly: a review of four unresolved questions.

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