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      Association between rs9930506 polymorphism of the fat mass & obesity-associated ( FTO) gene & onset of obesity in Polish adults

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          Abstract

          Background & objectives:

          The fat mass and obesity-associated ( FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults.

          Methods:

          The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m 2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism.

          Results:

          It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes.

          Interpretation & conclusions:

          This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.

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          Most cited references25

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          The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.

          Variants in the FTO (fat mass and obesity associated) gene are associated with increased body mass index in humans. Here, we show by bioinformatics analysis that FTO shares sequence motifs with Fe(II)- and 2-oxoglutarate-dependent oxygenases. We find that recombinant murine Fto catalyzes the Fe(II)- and 2OG-dependent demethylation of 3-methylthymine in single-stranded DNA, with concomitant production of succinate, formaldehyde, and carbon dioxide. Consistent with a potential role in nucleic acid demethylation, Fto localizes to the nucleus in transfected cells. Studies of wild-type mice indicate that Fto messenger RNA (mRNA) is most abundant in the brain, particularly in hypothalamic nuclei governing energy balance, and that Fto mRNA levels in the arcuate nucleus are regulated by feeding and fasting. Studies can now be directed toward determining the physiologically relevant FTO substrate and how nucleic acid methylation status is linked to increased fat mass.
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            Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO.

            The human obesity susceptibility gene, FTO, encodes a protein that is homologous to the DNA repair AlkB protein. The AlkB family proteins utilize iron(II), alpha-ketoglutarate (alpha-KG) and dioxygen to perform oxidative repair of alkylated nucleobases in DNA and RNA. We demonstrate here the oxidative demethylation of 3-methylthymine (3-meT) in single-stranded DNA (ssDNA) and 3-methyluracil (3-meU) in single-stranded RNA (ssRNA) by recombinant human FTO protein in vitro. Both human and mouse FTO proteins preferentially repair 3-meT in ssDNA over other base lesions tested. They showed negligible activities against 3-meT in double-stranded DNA (dsDNA). In addition, these two proteins can catalyze the demethylation of 3-meU in ssRNA with a slightly higher efficiency over that of 3-meT in ssDNA, suggesting that methylated RNAs are the preferred substrates for FTO.
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              Obesity-Associated Oxidative Stress: Strategies Finalized to Improve Redox State

              Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J. Med. Res
                IJMR
                The Indian Journal of Medical Research
                Medknow Publications & Media Pvt Ltd (India )
                0971-5916
                March 2016
                : 143
                : 3
                : 281-287
                Affiliations
                [1] Department of Pharmacogenomics, Division of Biochemistry & Clinical Chemistry, Medical University of Warsaw, Warsaw, Poland
                [* ] National Food & Nutrition Institute, Warsaw, Poland
                Author notes
                Reprint requests: Dr Małgorzata Wrzosek, Department of Pharmacogenomics, Division of Biochemistry & Clinical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha St. 1, 02-097 Warsaw, Poland e-mail: malgorzata.wrzosek@ 123456wum.edu.pl
                Article
                IJMR-143-281
                10.4103/0971-5916.182617
                4892073
                27241640
                5bb744c1-4a63-4de5-971d-cbc7cb1e3bd8
                Copyright: © Indian Journal of Medical Research

                This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 26 February 2014
                Categories
                Original Article

                Medicine
                adults,bmi,fto gene,obese,obesity,polymorphism
                Medicine
                adults, bmi, fto gene, obese, obesity, polymorphism

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