Keywords
rs2241766
allelic frequency
obesity
metabolic disorders
How to Cite
Abstract
Adiponectin is secreted by fat cells and appears to exert favorable metabolic effects. Some polymorphisms in ADIPOQ gene might be associated with obesity and cardiometabolic risk. The aim of this study was to evaluate the possible association of the polymorphism rs2241766 (ADIPOQ45 T/G) with the obese phenotype in a population of Maracaibo, Zulia state. The polymorphism was investigated in groups of obese (OB) and nonobese (No OB) individuals by PCR-RFLP. The genotypic frequency of rs2241766 polymorphism in the population was 80% for ADIPOQ45 T/T homozygous variant and 20% for ADIPOQ45 T/G heterozygous variant. The ADIPOQ45 homozygous genotype G/G was not found in this study. The allele frequencies of ADIPOQ45 T and G were 90% and 10%, respectively. Although ADIPOQ45 G allelic frequency was higher in the OB group, genotypic and allelic homogeneous distribution between OB and No OB groups support the lack of association of a particular allele with obesity. The ADIPOQ45 T/G genotype exhibited higher values in anthropometric indicators of obesity, serum lipid levels, basal glycemia, blood pressure and low serum HDL-cholesterol, revealing an unfavorable metabolic profile compared to individuals with ADIPOQ 45 T/T genotype, no significant differences between genotypes was found. This preliminary study established that the population evaluated exhibited an ADIPOQ 45 allelic frequency similar to that reported in European populations. The results of this study are consistent with research indicating modest effects of heterozygous genotype ADIPOQ45 T/G on obesity and other metabolic disorders.
References
OMS. Obesidad y sobrepeso [Internet]. Nota descriptiva. 2018 [cited 2022 Ago 30]. Available from: https://www.who.int/es/news-room/fact-sheets/detail/obesity-and-overweight
Friedrich MJ. Epidemic of obesity expands its spread to developing countries. Vol. 287, JAMA. United States; 2002. p. 1382–6.
Salud OP de la. Prevención de la Obesidad [Internet]. [cited 2022 Jul 6]. Available from: https://www.paho.org/es/temas/prevencion-obesidad
Nieto-Martínez R, González-Rivas JP, Ugel E, Brajkovich I, Risquez A, Garvey WT, et al. Application Of The Aace/Ace Advanced Framework For The Diagnosis Of Obesity And Cardiometabolic Disease Staging In A General Population From 3 Regions Of Venezuela: The Vemsols Study Results. Endocr Pract [Internet]. 2018;24(1):6–13. Available from: https://www.sciencedirect.com/science/article/pii/S1530891X2039354X
Arráiz N. Obesidad: Bases Moleculares. Primera. Mérida, Venezuela: Ediciones del Vice-Rectorado Académico, Universidad del Zulia. Editorial Venezolana, C.A.; 2007.
Moreno-Mascareño D, Magaña-Gómez J. Adiponectina, obesidad y síndrome metabólico: una relación para profundizar. RevMed UAS Nueva Época. 2012;3:29–39.
Salas-Salvadó J, Rubio MA, Barbany M, Moreno B, de la SEEDO* GC. Consenso SEEDO 2007 para la evaluación del sobrepeso y la obesidad y el establecimiento de criterios de intervención terapéutica. Med Clin (Barc) [Internet]. 2007;128(5):184–96. Available from: https://www.elsevier.es/es-revista-medicina-clinica-2-articulo-consenso-seedo-2007-evaluacion-del-13098399
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001 Aug;7(8):941–6.
Elissondo N, Rosso LG, Maidana P, Brites F. Adiponectina: una adipocitoquina con múltiples funciones protectoras. Acta Bioquímica Clínica Latinoam. 2008;42(1):17–33.
Saito K, Tobe T, Minoshima S, Asakawa S, Sumiya J, Yoda M, et al. Organization of the gene for gelatin-binding protein (GBP28). Gene. 1999 Mar;229(1–2):67–73.
Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes. 2000;24(7):861–8.
Howlader M, Sultana MI, Akter F, Hossain MM. Adiponectin gene polymorphisms associated with diabetes mellitus: A descriptive review. Heliyon. 2021 Aug;7(8):e07851.
Jee SH, Sull JW, Lee J-E, Shin C, Park J, Kimm H, et al. Adiponectin concentrations: a genome-wide association study. Am J Hum Genet. 2010 Oct;87(4):545–52.
Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, et al. Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes. J Biol Chem. 2003 Oct 10;278(41):40352–63.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: Close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930–5.
Punyadeera C, Zorenc A, Koopman R, McAinch A, Smit E, Manders R, et al. The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle. Eur J Endocrinol [Internet]. 2005 [cited 2022 Ago 30];152(3):427–36. Available from: https://eje.bioscientifica.com/view/journals/eje/152/3/1520427.xml
Henneman P, Aulchenko YS, Frants RR, Zorkoltseva I V., Zillikens MC, Frolich M, et al. Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits. Diabetes Care. 2010 Apr;33(4):908–13.
Menzaghi C, Trischitta V, Doria A. Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes. 2007 May;56(5):1198–209.
Ling H, Waterworth DM, Stirnadel HA, Pollin TI, Barter PJ, Kesäniemi YA, et al. Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: The GEMS study. Obesity. 2009 Apr;17(4):737–44.
Sánchez MP, Prieto C, Mujica E, Vergara K, Valencia E, Villalobos E, et al. Association between +45T>G adiponectin polymorphism gene and type 2 diabetes mellitus and metabolic syndrome in a Venezuelan population. F1000Research. 2019;8:292.
Heid IM, Henneman P, Hicks A, Coassin S, Winkler T, Aulchenko YS, et al. Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals. Atherosclerosis. 2010 Feb;208(2):412–20.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge. Clin Chem. 1972;18(6):499–502.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res [Internet]. 1988 Feb 11;16(3):1215. Available from: https://pubmed.ncbi.nlm.nih.gov/3344216
Sabouri S, Ghayour-Mobarhan M, Mouhebati M, Hassani M, Kassaeian J, Tatari F, et al. Association between 45T/G polymorphism of adiponectin gene and coronary artery disease in an iranian population. ScientificWorldJournal. 2011 Jan 5;11:93–101.
Foucan L, Maimaitiming S, Larifla L, Hedreville S, Deloumeaux J, Joannes MO, et al. Adiponectin gene variants, adiponectin isoforms and cardiometabolic risk in type 2 diabetic patients. J Diabetes Investig. 2014;5(2):192–8.
Wu J, Liu Z, Meng K, Zhang L. Association of Adiponectin gene (ADIPOQ) rs2241766 polymorphism with obesity in adults: A meta-analysis. PLoS One. 2014;9(4):e95270.
Cesari M, Narkiewicz K, De Toni R, Aldighieri E, Williams CJ, Rossi GP. Heritability of Plasma Adiponectin Levels and Body Mass Index in Twins. J Clin Endocrinol Metab [Internet]. 2007 Aug [cited 2022 Ago 30];92(8):3082–8. Available from: https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2007-0403
Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, et al. Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation. 2002 Jun;105(24):2893–8.
Snijder MB, Heine RJ, Seidell JC, Bouter LM, Stehouwer CDA, Nijpels G, et al. Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women the hoorn study. Diabetes Care. 2006 Nov;29(11):2498–503.
Fumeron F, Aubert R, Siddiq A, Betoulle D, Péan F, Hadjadj S, et al. Adiponectin Gene Polymorphisms and Adiponectin Levels Are Independently Associated with the Development of Hyperglycemia during a 3-Year Period: The Epidemiologic Data on the Insulin Resistance Syndrome Prospective Study. Diabetes. 2004 Apr;53(4):1150–7.
Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003 Jun 12;423(6941):762–9.
Gupta V, Khadgawat R, Tony Ng HK, Walia GK, Kalla L, Rao VR, et al. Association of TCF7L2 and ADIPOQ with body mass index, waist-hip ratio, and systolic blood pressure in an endogamous ethnic group of India. Genet Test Mol Biomarkers. 2012 Aug 1;16(8):948–51.
Mackevics V, Heid IM, Wagner SA, Cip P, Doppelmayr H, Lejnieks A, et al. The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. Eur J Hum Genet. 2006 Mar;14(3):349–56.
Peters KE, Beilby J, Cadby G, Warrington NM, Bruce DG, Davis WA, et al. A comprehensive investigation of variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/R2), and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndrome. BMC Med Genet. 2013 Jan;14:15.
Lara-Castro C, Doud EC, Tapia PC, Munoz AJ, Fernandez JR, Hunter GR, et al. Adiponectin multimers and metabolic syndrome traits: Relative adiponectin resistance in African Americans. Obesity. 2008 Dec;16(12):2616–23.
Torres-Castillo N, Campos-Perez W, Rodriguez-Echevarria R, Rodriguez-Reyes SC, Martinez-Lopez E. A Metabolically Unhealthy Phenotype Is Associated with ADIPOQ Genetic Variants and Lower Serum Adiponectin Levels. Lifestyle Genomics [Internet]. 2020;13(6):172–9. Available from: https://www.karger.com/DOI/10.1159/000510021
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2022 María Patricia Sanchez, Nailet Arráiz, Karen Cubillan, Vanessa Matheus, Deirymar Montero