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      The Association Between the Uncoupling Protein-1 Gene A-3826G Polymorphism and High-density Lipoprotein Cholesterol in A General Japanese Population: A Consideration of the Obesity Status

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          Abstract

          Background

          Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects.

          Methods

          Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m 2, and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol.

          Results

          The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group.

          Conclusions

          The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol.

          Keywords

          Obesity; Body mass index; HDL-C; Atherosclerotic risk

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          Most cited references19

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          WHO recognition of the global obesity epidemic.

          The recognition of obesity as a disease was in theory established in 1948 by WHO's (World Health Organization) taking on the International Classification of Diseases but the early highlighting of the potential public health problem in the United States and the United Kingdom 35 years ago was considered irrelevant elsewhere. The medical profession disregarded obesity as important despite the new evidence and WHO data set out in the 1980s. Only in 1995 did WHO find greater problems of overweight than underweight in many developing countries but it required the first special obesity consultation in 1997 and particularly the Millennium burden of disease analyses to suddenly highlight its crucial role in the current unmanageable and escalating medical costs globally. Governments now recognize the overwhelming industrial developments that guarantee an escalating epidemic but neither they nor WHO know how to engage in changing the societal framework to promote routine spontaneous physical activity and a transformation of the food system so that low energy-density food of high nutrient quality becomes the norm.
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            Diagnostic criteria for dyslipidemia. Executive summary of Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of atherosclerotic cardiovascular diseases for Japanese.

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              Gene-environment interactions in obesity.

              Obesity is a global and growing problem. The detrimental health consequences of obesity are significant and include co-morbidities such as diabetes, cancer and coronary heart disease. The marked rise in obesity observed over the last three decades suggests that behavioural and environmental factors underpin the chronic mismatch between energy intake and energy expenditure. However, not all individuals become obese, suggesting that there is considerable variation in responsiveness to 'obesogenic' environments. Some individuals defend easily against a propensity to accumulate fat mass and become overweight whilst others are predisposed to gain weight, possibly as a function of genotype. The genetic contribution to obesity is well established. Common obesity is polygenic, involving complex gene-gene and gene-environment interactions, and it is these interactions that produce the multi-factorial obese phenotypes. Candidate gene variants for polygenic obesity appear to disrupt pathways involved in the regulation of energy intake and expenditure and include adrenergic receptors, uncoupling proteins, PPARG, POMC, MC4R and a set of single nucleotide polymorphisms in the FTO locus. Notably, the FTO gene is the most robust gene for common obesity characterised to date, and recent data shows that the FTO locus seems to confer risk of obesity through increasing energy intake and reduced satiety. Gene variants involved in pathways regulating addiction and reward behaviours may also play a role in predisposition to obesity. Understanding the routes through which the genotype is expressed will ultimately provide opportunities for developing strategies to intervene, as the interaction between genotype and environment is potentially modifiable through behaviour change. Copyright (c) 2010 S. Karger AG, Basel.
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                Author and article information

                Journal
                J Clin Med Res
                Elmer Press
                Journal of Clinical Medicine Research
                Elmer Press
                1918-3003
                1918-3011
                December 2011
                10 November 2011
                : 3
                : 6
                : 319-324
                Affiliations
                [a ]Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
                [b ]Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-Tochigi, Japan
                [c ]Department of Food Science and Nutrition, University of Hyogo, Hyogo, Japan
                Author notes
                [d ]Corresponding author: Kazuhiko Kotani, MD, PhD, Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1 - 1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan. Email: kazukotani@ 123456jichi.ac.jp
                Article
                10.4021/jocmr738w
                3279477
                22393344
                3ae88ac9-540b-46bc-86de-a3f7f2973411
                Copyright 2011, Kotani et al.

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

                History
                : 31 October 2011
                Categories
                Short Communication

                Medicine
                Medicine

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