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      ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1

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          Abstract

          Background

          In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253 ) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders.

          Methods

          We studied 329 non-related adults (33.1% men and 66.9% women), aged 18–36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m 2), overweight (BMI ≥25.1–29.9 kg/m 2) subjects, and obese (≥30 kg/m 2).

          Results

          In the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele.

          Conclusion

          The results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.

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          Most cited references61

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          Obesity preventing and managing the globalepidemic, report of a WHO consultation

          WHO WHO (2000)
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            Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity.

            The beta 3-adrenergic receptor, located mainly in adipose tissue, is involved in the regulation of lipolysis and thermogenesis. The potential relevance of this receptor to obesity in humans led us to screen obese French patients for a recently identified mutation in the gene for the receptor. We used the polymerase chain reaction to amplify a region of the gene for the beta 3-adrenergic receptor encoding amino acid residues 27 to 110 in genomic DNA extracted from leukocytes from 185 patients with morbid obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], > 40) and 94 normal subjects. A mutation resulting in the replacement of tryptophan by arginine at position 64 (Trp64Arg) was detected by an analysis of restriction-fragment-length polymorphisms with the use of the endonuclease BstNl, which discriminates between the normal and mutant sequences. The frequency of the Trp64Arg allele was similar in the morbidly obese patients and the normal subjects (0.08 and 0.10, respectively). However, the patients with morbid obesity who were heterozygous for the Trp64Arg mutation had an increased capacity to gain weight; the mean weight in the 14 heterozygous patients was 140 kg, as compared with 126 kg in the 171 patients without the mutation (P = 0.03). There were no homozygotes in this sample. The cumulative 25-year change in weight (from the age of 20 years) was 67 kg in the Trp64Arg heterozygotes, as compared with 51 kg in those without the mutation. The maximal weight differential (the maximal lifetime weight minus the weight at 20 years of age) in the Trp64Arg heterozygotes was 74 kg, as compared with 59 kg in the patients without the mutation (P = 0.02). People with the Trp64Arg mutation of the gene for the beta 3-adrenergic receptor may have an increased capacity to gain weight.
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              Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function.

              Catecholamines play a central role in the regulation of energy expenditure, in part by stimulating lipid mobilization through lipolysis in fat cells. The beta-2 adrenoceptor (BAR-2) is a major lipolytic receptor in human fat cells. To determine whether known polymorphisms in codons 16, 27, and 164 of this receptor play a role in obesity and subcutaneous adipocyte BAR-2 lipolytic function, we investigated a group of 140 women with a large variation in body fat mass. Only the polymorphisms in codons 16 and 27 were common in the study population. The Gln27Glu polymorphism was markedly associated with obesity with a relative risk for obesity of approximately 7 and an odds ratio of approximately 10. Homozygotes for Glu27 had an average fat mass excess of 20 kg and approximately 50% larger fat cells than controls. However, no significant association with changes in BAR-2 function was observed. The Arg16Gly polymorphism was associated with altered BAR-2 function with Gly16 carriers showing a fivefold increased agonist sensitivity and without any change in BAR-2 expression. However, it was not significantly linked with obesity. These findings suggest that genetic variability in the human BAR-2 gene could be of major importance for obesity, energy expenditure, and lipolytic BAR-2 function in adipose tissue, at least in women.
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                Author and article information

                Contributors
                mdaghestani@ksu.edu.sa
                mhdaghestani@uqu.edu.sa
                mdaghist@hotmail.com
                adalee@kfshrc.edu.sa
                hildahafez@hotmail.com
                mahaalamin@yahoo.com
                aswarsy@ksu.edu.sa
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                27 March 2018
                27 March 2018
                2018
                : 17
                : 58
                Affiliations
                [1 ]ISNI 0000 0004 1773 5396, GRID grid.56302.32, Department of Zoology, , Center for Scientific and Medical Female Colleges, King Saud University, ; P.O. Box 22455, Riyadh, 11495 Saudi Arabia
                [2 ]ISNI 0000 0000 9137 6644, GRID grid.412832.e, Department of Obstetrics and Gynecology, , Umm-Al-Qura University, ; P.O.Box 424, Makkah, 21955 Saudi Arabia
                [3 ]ISNI 0000 0004 1790 7311, GRID grid.415254.3, Department of Surgery, , King Abdulaziz Medical City, National Guard Health Affairs, ; P.O.Box, Jeddah, 9515 Saudi Arabia
                [4 ]ISNI 0000 0001 2191 4301, GRID grid.415310.2, Department of Biostatistics, Epidemiology and Scientific Computing, , King Faisal Specialist Hospital and Research Center, ; P.O. Box3354, Riyadh, 11211 Saudi Arabia
                [5 ]ISNI 0000 0004 0639 9286, GRID grid.7776.1, Virology and Immunology Unit, Cancer Biology Department, , National Cancer Institute Cairo University, ; Cairo, Egypt
                [6 ]ISNI 0000 0004 1773 5396, GRID grid.56302.32, Department of Zoology, Faculty of Sciences, , King Saud University, ; P.O. Box 22452, Riyadh, 11495 Saudi Arabia
                [7 ]ISNI 0000 0004 1773 5396, GRID grid.56302.32, Senior Scientist, Central Laboratory, Center for Scientific and Medical Female Colleges, , King Saud University, ; P.O. Box 22455, Riyadh, 11495 Saudi Arabia
                Author information
                http://orcid.org/0000-0001-6957-203X
                Article
                679
                10.1186/s12944-018-0679-7
                5870215
                29587766
                33daccb8-8e78-41dc-94dc-554d64b9ad56
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 September 2017
                : 19 February 2018
                Funding
                Funded by: Deanship of Scientific Research, King Saud University in Riyadh, Saudi Arabia.
                Award ID: research group no. RGP-VPP-068
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Biochemistry
                β1 adrenoceptor,β3 adrenoceptor,dyslipidaemias,polymorphism,obesity,saudi population,χ2 chi square

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