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      Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans

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          Abstract

          Objective

          The role of genetic factors in the development of obesity is largely unreported in Sri Lankans. The Q223R (rs1137101) single nucleotide polymorphism (SNP) of the leptin receptor ( LEPR) gene has been associated with obesity measures in various ethnicities. We investigated the association of the Q223R polymorphism with obesity related anthropometric measures and biochemical parameters fasting blood glucose and lipid profile in a sample of 530 Sri Lankan adult subjects (age 18–70 years) representing both urban and rural areas of residence.

          Results

          The LEPR Q223R variant G allele frequency was 0.54. The polymorphism was associated with body mass index ( p = 0.04) and waist circumference ( p = 0.02) measures in overweight and obese (BMI ≥ 25 kgm −2) subjects with the variant allele conferring a greater risk of adiposity. Residency in urban areas eliminated the protective effect of the non-risk genotype (AA) in the development of obesity.

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          Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.

          I. Sadaf Farooqi, Teresia Wangensteen, Stephan Collins … (2007)
          A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined. We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives. Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations--7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency. The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism. Copyright 2007 Massachusetts Medical Society.
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            Prevalence of overweight and obesity in Sri Lankan adults.

            Denny G. Constantine, Brent D. Matthews, M Jayawardena … (2010)
            The aim of the study was to determine the prevalence of overweight, obesity and abdominal obesity, and the underlying socio-demographic correlates among Sri Lankan adults. Data were from 4532 adults aged ≥18 years randomly selected for a national level study on diabetes and cardiovascular disease. Weight, height and waist circumference (WC) were measured and body mass index (BMI) calculated. The mean (95% confidence interval) BMI and WC were 21.1 kg m(-2) (20.9-21.3), 22.3 kg m(-2) (22.1-22.4) and 78.0 cm (77.5-78.6) and 77.5 cm (77.0-78.0) for males and females, respectively. According to the proposed World Health Organization cut-off values for Asians, the percentage of Sri Lankan adults in the overweight, obese and centrally obese categories were 25.2%, 9.2% and 26.2%, respectively. Based on the cut-offs for Caucasians, these were 16.8%, 3.7% and 10.8%. Our findings were compatible with prevalence of obesity in regional countries. In addition, female sex, urban living, higher education, higher income and being in the middle age were shown to be associated with overweight and obesity in Sri Lankans. In conclusion, we have documented a relatively high prevalence of overweight and obesity, particularly, abdominal obesity among adults in Sri Lanka which is a middle-income country. Urgent public health interventions are needed to control the problem at an early stage. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.
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              A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women.

              R. Eastell, Cheryl Quinton, Alice W. Lee … (2001)
              The human leptin (obese) receptor gene contains a number of single nucleotide polymorphisms, including GLN223ARG, which changes an amino acid on the extracellular region common to all isoforms of the receptor. Here, we demonstrate that, in postmenopausal Caucasian women, genotypes at that locus are associated with differences in body mass index (BMI), fat mass and serum leptin levels. Measurement of serum leptin-binding activity indicates that this may reflect changed receptor function associated with genotype. These observations indicate that functional variations in the leptin receptor gene are important factors in the regulation of adiposity and BMI.
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                Author and article information

                Contributors
                Y. A. Illangasekera:
                ORCID: http://orcid.org/0000-0002-7466-5502
                yasi04@gmail.com
                Journal
                Journal ID (nlm-ta): BMC Res Notes
                Journal ID (iso-abbrev): BMC Res Notes
                Title: BMC Research Notes
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-0500
                Publication date (Electronic): 16 January 2020
                Publication date PMC-release: 16 January 2020
                Publication date Collection: 2020
                Volume: 13
                Electronic Location Identifier: 34
                Affiliations
                [1 ]ISNI 0000 0000 9816 8637, GRID grid.11139.3b, Dept. of Pharmacology, Faculty of Medicine, , University of Peradeniya, ; Peradeniya, Sri Lanka
                [2 ]ISNI 0000 0000 9816 8637, GRID grid.11139.3b, Dept. of Community Medicine, Faculty of Medicine, , University of Peradeniya, ; Peradeniya, Sri Lanka
                [3 ]ISNI 0000 0004 0469 8549, GRID grid.464673.4, Dept. of Diabetes and Endocrinology, Kings Mill Hospital, , Sherwood Forest Hospitals NHS Foundation Trust, ; Sutton-in-Ashfield, UK
                [4 ]ISNI 0000 0001 0303 540X, GRID grid.5884.1, Biomolecular Sciences Research Centre, Faculty of Health and Wellbeing, , Sheffield Hallam University, ; Sheffield, UK
                Author information
                http://orcid.org/0000-0002-7466-5502
                Article
                Publisher ID: 4898
                DOI: 10.1186/s13104-020-4898-4
                PMC ID: 6966896
                PubMed ID: 31948470
                SO-VID: 172e9ba4-6c92-494f-9266-c5983add4080
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                Date received : 4 August 2019
                Date accepted : 8 January 2020
                Funding
                Funded by: Ministry of Higher Education, Sri Lanka
                Award ID: PDN/0-Med/N4
                Categories
                Subject: Research Note
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Medicine
                Keywords: obesity,genetics,polymorphism,leptin receptor
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: obesity, genetics, polymorphism, leptin receptor

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