DOI: https://doi.org/10.14710/jnc.v15i4.54318

ASSOCIATION BETWEEN THE ADRB2 GLN27GLU (rs1042714) VARIANT AND OBESITY: A NARRATIVE REVIEW

1Department of Nutrition Science, Faculty of Medicine, Universitas Diponegoro, Semarang, Jawa Tengah, Indonesia

2Department of Medicine, Faculty of Medicine, Universitas Diponegoro, Semarang, Jawa Tengah, Indonesia

Received: 26 Nov 2025; Revised: 19 Jun 2026; Accepted: 17 Jul 2026; Available online: 30 Oct 2026; Published: 30 Oct 2026.

Citation Format:
Abstract

ABSTRACT

Background: Obesity is a global health crisis underpinned by a complex interplay between genetics and environment. The β2-adrenergic receptor gene (ADRB2), a key regulator of lipolysis and energy expenditure, is a strong candidate for obesity susceptibility. The ADRB2 Gln27Glu (rs1042714) polymorphism has been widely studied, but its association with obesity and metabolic traits remains controversial, with contradictory findings across the literature.

Objectives: This narrative review aims to summarize and critically analyze the scientific literature regarding the ADRB2 rs1042714 variant.

Methods: A narrative literature review was conducted using the Google Scholar, ScienceDirect, Scopus, and PubMed databases. Inclusion criteria selected primary research articles published in English that investigated the association between ADRB2 rs1042714, obesity, body composition, and interactions with diet or physical activity.

Results: The literature review confirms a profound lack of consensus. Some studies associate the Glu27 (G allele) with increased obesity risk, while others associate the Gln27 (C allele) with risk or find the G allele to be protective. These discrepancies are largely explained by three factors: 1) Ethnicity; 2) Gen-diet interaction; and 3) Gene-exercise interaction.

Conclusion: The ADRB2 Gln27Glu polymorphism is not a deterministic factor for obesity. Its association with adiposity is highly context-dependent, critically modulated by genetic ancestry, dietary macronutrient composition, and physical activity levels. The contradictions in the literature highlight the necessity of moving from simple association studies to more nuanced gene-environment interaction models to understand the variant's true clinical relevance.

Keywords: ADRB2; rs1042714; Gln27Glu; obesity; lipolysis

Fulltext View|Download Email colleagues
Keywords: ADRB2; rs1042714; Gln27Glu; obesity; lipolysis

Article Metrics:

Article Info
Section: Articles
Language : EN
  1. Zhang H, Wu J, Yu L. Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis. PLoS One. 2014;9(6):e100489. doi: 10.1371/journal.pone.0100489PubMedPMID:24960039
  2. Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022 Aug;133:155217. doi: 10.1016/j.metabol.2022.155217
  3. McPherson R. Genetic contributors to obesity. Canadian Journal of Cardiology. 2007 Aug;23:23A-27A. doi: 10.1016/S0828-282X(07)71002-4
  4. Bouchard C. Genetics of Obesity: What We Have Learned Over Decades of Research. Obesity. 2021 May 26;29(5):802–20. doi: 10.1002/oby.23116
  5. Mahmoud R, Kimonis V, Butler MG. Genetics of Obesity in Humans: A Clinical Review. Int J Mol Sci. 2022 Sep 20;23(19). doi: 10.3390/ijms231911005PubMedPMID:36232301
  6. da Fonseca ACP, Assis IS da S, Salum KCR, Palhinha L, Abreu G de M, Zembrzuski VM, et al. Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications. Front Genet. 2024 May 22;15. doi: 10.3389/fgene.2024.1363417
  7. Jesus ÍC de, Alle LF, Tureck LV, Silva LR da, Lopes WA, Moraes Junior FB de, et al. ADRB2 GLN27GLU POLYMORPHISM ASSOCIATED WITH ADIPOSITY INDICATORS AND IL-10 IN ADOLESCENTS. Revista Brasileira de Medicina do Esporte. 2019 Aug;25(4):322–7. doi: 10.1590/1517-869220192504214836
  8. Collins S. β-adrenoceptor signaling networks in adipocytes for recruiting stored fat and energy expenditure. Front Endocrinol (Lausanne). 2011;2. doi: 10.3389/fendo.2011.00102
  9. Ishida Y, Matsushita M, Yoneshiro T, Saito M, Fuse S, Hamaoka T, et al. Genetic evidence for involvement of β2-adrenergic receptor in brown adipose tissue thermogenesis in humans. Int J Obes. 2024 Aug 17;48(8):1110–7. doi: 10.1038/s41366-024-01522-6
  10. Arner P, Hoffstedt J. Adrenoceptor genes in human obesity. J Intern Med. 1999 Jun 25;245(6):667–72. doi: 10.1046/j.1365-2796.1999.00495.x
  11. Moore GE, Shuldiner AR, Zmuda JM, Ferrell RE, McCole SD, Hagberg JM. Obesity gene variant and elite endurance performance. Metabolism. 2001 Dec;50(12):1391–2. doi: 10.1053/meta.2001.28140
  12. Jocken JWE, Blaak EE, Schiffelers S, Arner P, van Baak MA, Saris WHM. Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation. Int J Obes. 2007 May 28;31(5):813–9. doi: 10.1038/sj.ijo.0803499
  13. Takenaka A, Nakamura S, Mitsunaga F, Inoue-Murayama M, Udono T, Suryobroto B. Human-Specific SNP in Obesity Genes, Adrenergic Receptor Beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during Primate Evolution. PLoS One. 2012 Aug 24;7(8):e43461. doi: 10.1371/journal.pone.0043461
  14. Salas-Martínez MG, Saldaña-Alvarez Y, Cordova EJ, Mendiola-Soto DK, Cid-Soto MA, Luckie-Duque A, et al. Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population. PLoS One. 2019 Dec 2;14(12):e0225030. doi: 10.1371/journal.pone.0225030
  15. Saliba LF, Reis RS, Brownson RC, Hino AA, Tureck L V., Valko C, et al. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women. Genet Mol Biol. 2014;37(1):15–22. doi: 10.1590/S1415-47572014000100005
  16. Sarpeshkar V, Bentley DJ. Adrenergic-β2 receptor polymorphism and athletic performance. J Hum Genet. 2010 Aug 30;55(8):479–85. doi: 10.1038/jhg.2010.42
  17. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, et al. FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012 Mar 7;15(3):279–91. doi: 10.1016/j.cmet.2011.12.018PubMedPMID:22405066
  18. Mullins GR, Wang L, Raje V, Sherwood SG, Grande RC, Boroda S, et al. Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes. Proceedings of the National Academy of Sciences. 2014 Dec 9;111(49):17450–5. doi: 10.1073/pnas.1410530111
  19. Jönsson C, Castor Batista AP, Kjølhede P, Strålfors P. Insulin and β-adrenergic receptors mediate lipolytic and anti-lipolytic signalling that is not altered by type 2 diabetes in human adipocytes. Biochemical Journal. 2019 Oct 15;476(19):2883–908. doi: 10.1042/BCJ20190594
  20. Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, et al. Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation. Cell Metab. 2020 Aug;32(2):287-300.e7. doi: 10.1016/j.cmet.2020.07.005
  21. Arner P, Hoffstedt J. Adrenoceptor genes in human obesity. J Intern Med. 1999 Jun 25;245(6):667–72. doi: 10.1046/j.1365-2796.1999.00495.x
  22. Kunnas T, Lahtio R, Kortelainen ML, Kalela A, Nikkari ST. Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women. Lipids Health Dis. 2009;8(1):43. doi: 10.1186/1476-511X-8-43
  23. Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human. Cell. 2012 Jul;150(2):366–76. doi: 10.1016/j.cell.2012.05.016
  24. Salas-Martínez MG, Saldaña-Alvarez Y, Cordova EJ, Mendiola-Soto DK, Cid-Soto MA, Luckie-Duque A, et al. Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population. PLoS One. 2019;14(12):e0225030. doi: 10.1371/journal.pone.0225030PubMedPMID:31790415
  25. Beason TS, Bunker CH, Zmuda JM, Wilson JW, Patrick AL, Wheeler VW, et al. ADRB2 gene variants, dual-energy x-ray absorptiometry body composition, and hypertension in Tobago men of African descent. Metabolism. 2011 May;60(5):698–705. doi: 10.1016/j.metabol.2010.07.004
  26. de Luis DA, Izaola O, Primo D, Gómez JJL. Role of beta-2 adrenergic receptor polymorphism (rs1042714) on body weight and glucose metabolism response to a meal-replacement hypocaloric diet. Nutrition. 2023 Dec;116:112170. doi: 10.1016/j.nut.2023.112170
  27. Takenaka A, Nakamura S, Mitsunaga F, Inoue-Murayama M, Udono T, Suryobroto B. Human-Specific SNP in Obesity Genes, Adrenergic Receptor Beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during Primate Evolution. PLoS One. 2012 Aug 24;7(8):e43461. doi: 10.1371/journal.pone.0043461
  28. Drolet R, Richard C, Sniderman AD, Mailloux J, Fortier M, Huot C, et al. Hypertrophy and hyperplasia of abdominal adipose tissues in women. Int J Obes. 2008 Feb 28;32(2):283–91. doi: 10.1038/sj.ijo.0803708
  29. Giralt M, Villarroya F. White, Brown, Beige/Brite: Different Adipose Cells for Different Functions? Endocrinology. 2013 Sep 1;154(9):2992–3000. doi: 10.1210/en.2013-1403
  30. Frühbeck G, Méndez-Giménez L, Fernández-Formoso JA, Fernández S, Rodríguez A. Regulation of adipocyte lipolysis. Nutr Res Rev. 2014 Jun 28;27(1):63–93. doi: 10.1017/S095442241400002X
  31. Mori Y, Kim-Motoyama H, Ito Y, Katakura T, Yasuda K, Ishiyama-Shigemoto S, et al. The Gln27Glu β2-Adrenergic Receptor Variant Is Associated with Obesity Due to Subcutaneous Fat Accumulation in Japanese Men. Biochem Biophys Res Commun. 1999 Apr;258(1):138–40. doi: 10.1006/bbrc.1999.0607
  32. Kachkovska V. Association between Gln27Glu Polymorphism in the B2 Adrenergic Receptor Gene and Obesity Risk in Patients with Early-Onset and Late-Onset Bronchial Asthma. Georgian Med News. 2023;(340–341):254–8. PubMed PMID: 37805907
  33. Lange LA, Norris JM, Langefeld CD, Nicklas BJ, Wagenknecht LE, Saad MF, et al. Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study. Int J Obes. 2005 May 18;29(5):449–57. doi: 10.1038/sj.ijo.0802883
  34. Large V, Hellström L, Reynisdottir S, Lönnqvist F, Eriksson P, Lannfelt L, et al. Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. Journal of Clinical Investigation. 1997 Dec 15;100(12):3005–13. doi: 10.1172/JCI119854
  35. Zhang H, Wu J, Yu L. Association of Gln27Glu and Arg16Gly Polymorphisms in Beta2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis. PLoS One. 2014 Jun 24;9(6):e100489. doi: 10.1371/journal.pone.0100489
  36. Mori Y, Kim-Motoyama H, Ito Y, Katakura T, Yasuda K, Ishiyama-Shigemoto S, et al. The Gln27Glu β2-Adrenergic Receptor Variant Is Associated with Obesity Due to Subcutaneous Fat Accumulation in Japanese Men. Biochem Biophys Res Commun. 1999 Apr;258(1):138–40. doi: 10.1006/bbrc.1999.0607
  37. Rooyen J, Pretorius P, Britz M, Huisman H, Schutte A, Towers G, et al. Genetic Polymorphisms of β 2 - and β 3 -Adrenergic Receptor Genes Associated with Characteristics of the Metabolic Syndrome in Black South African Women. Experimental and Clinical Endocrinology & Diabetes. 2008 Apr 7;116(04):236–40. doi: 10.1055/s-2007-992785
  38. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P. Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population. Int J Obes. 2000 Mar 13;24(3):382–7. doi: 10.1038/sj.ijo.0801168
  39. Saliba LF, Reis RS, Brownson RC, Hino AA, Tureck L V., Valko C, et al. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women. Genet Mol Biol. 2014;37(1):15–22. doi: 10.1590/S1415-47572014000100005
  40. Naka I, Hikami K, Nakayama K, Koga M, Nishida N, Kimura R, et al. A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations. Int J Obes. 2013 Sep 11;37(9):1204–10. doi: 10.1038/ijo.2012.206
  41. da Fonseca ACP, Assis IS da S, Salum KCR, Palhinha L, Abreu G de M, Zembrzuski VM, et al. Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications. Front Genet. 2024 May 22;15. doi: 10.3389/fgene.2024.1363417
  42. González Sánchez JL, Proenza AM, Martínez Larrad MT, Ramis JM, Fernández Pérez C, Palou A, et al. The glutamine 27 glutamic acid polymorphism of the β 2 ‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain. Clin Endocrinol (Oxf). 2003 Oct 18;59(4):476–81. doi: 10.1046/j.1365-2265.2003.01871.x
  43. DUARTE NL, COLAGIURI S, PALU T, WANG XL, WILCKEN DEL. Obesity, Type II diabetes and the β2 adrenoceptor gene Gln27Glu polymorphism in the Tongan population. Clin Sci. 2003 Mar 1;104(3):211–5. doi: 10.1042/cs1040211
  44. Martínez JA, Corbalán MS, Forga L, Marti A, Sánchez-Villegas A, Martínez-González MA. Obesity Risk Is Associated with Carbohydrate Intake in Women Carrying the Gln27Glu β2-Adrenoceptor Polymorphism. J Nutr. 2003 Aug;133(8):2549–54. doi: 10.1093/jn/133.8.2549
  45. Pereira T V., Mingroni‐Netto RC, Yamada Y. ADRB2 and LEPR Gene Polymorphisms: Synergistic Effects on the Risk of Obesity in Japanese. Obesity. 2011 Jul 10;19(7):1523–7. doi: 10.1038/oby.2010.322
  46. Kim SH, Kim DJ, Seo IA, Min YK, Lee MS, Kim KW, et al. Significance of [beta ]2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism. 2002 Jul;51(7):833–7. doi: 10.1053/meta.2002.33347
  47. Iwamoto N, Ogawa Y, Kajihara S, Hisatomi A, Yasutake T, Yoshimura T, et al. Gln27Glu β2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clinica Chimica Acta. 2001 Dec;314(1–2):85–91. doi: 10.1016/S0009-8981(01)00633-7
  48. Mori Y, Kim-Motoyama H, Ito Y, Katakura T, Yasuda K, Ishiyama-Shigemoto S, et al. The Gln27Glu β2-Adrenergic Receptor Variant Is Associated with Obesity Due to Subcutaneous Fat Accumulation in Japanese Men. Biochem Biophys Res Commun. 1999 Apr;258(1):138–40. doi: 10.1006/bbrc.1999.0607
  49. Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K. Association of polymorphisms in the ?2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus (Short Communication). Diabetologia. 1999 Jan 11;42(1):98–101. doi: 10.1007/s001250051120
  50. Kim SH, Kim DJ, Seo IA, Min YK, Lee MS, Kim KW, et al. Significance of [beta ]2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism. 2002 Jul;51(7):833–7. doi: 10.1053/meta.2002.33347
  51. Jalba MS, Rhoads GG, Demissie K. Association of Codon 16 and Codon 27 β2‐Adrenergic Receptor Gene Polymorphisms with Obesity: A Meta‐analysis. Obesity. 2008 Sep 6;16(9):2096–106. doi: 10.1038/oby.2008.327
  52. Ruiz JR, Larrarte E, Margareto J, Ares R, Labayen I. Role of β 2 ‐Adrenergic Receptor Polymorphisms on Body Weight and Body Composition Response to Energy Restriction in Obese Women: Preliminary Results. Obesity. 2011 Jan 6;19(1):212–5. doi: 10.1038/oby.2010.130
  53. Nanri H, Nishida Y, Nakamura K, Tanaka K, Naito M, Yin G, et al. Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study. Nutrients. 2016 Sep 6;8(9):545. doi: 10.3390/nu8090545
  54. Kunnas T, Lahtio R, Kortelainen ML, Kalela A, Nikkari ST. Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women. Lipids Health Dis. 2009;8(1):43. doi: 10.1186/1476-511X-8-43
  55. Prior SJ, Goldberg AP, Ryan AS. ADRB2 Haplotype Is Associated With Glucose Tolerance and Insulin Sensitivity in Obese Postmenopausal Women. Obesity. 2011 Feb 6;19(2):396–401. doi: 10.1038/oby.2010.197
  56. Schürks M, Kurth T, Ridker PM, Buring JE, Zee RYL. Association between polymorphisms in the beta2-adrenergic receptor gene with myocardial infarction and ischaemic stroke in women. Thromb Haemost. 2009 Feb;101(2):351–8. PubMed PMID: 19190821
  57. Atala MM, Goulart A, Guerra GM, Mostarda C, Rodrigues B, Mello PR, et al. Arg16Gly and Gln27Glu β2 adrenergic polymorphisms influence cardiac autonomic modulation and baroreflex sensitivity in healthy young Brazilians. Am J Transl Res. 2015;7(1):153–61. PubMed PMID: 25755837
  58. Shakhanova A, Aukenov N, Nurtazina A, Massabayeva M, Babenko D, Adiyeva M, et al. Association of polymorphism genes LPL , ADRB2 , AGT and AGTR1 with risk of hyperinsulinism and insulin resistance in the Kazakh population. Biomed Rep. 2020 Nov;13(5):35. doi: 10.3892/br.2020.1342PubMedPMID:32843963
  59. Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Pérusse L, Chagnon YC, et al. Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study. Metabolism. 2000 Aug;49(8):1063–70. doi: 10.1053/meta.2000.7708PubMedPMID:10954027
  60. Vardeny O, Detry MA, Moran JJM, Johnson MR, Sweitzer NK. The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker. J Cardiovasc Pharmacol. 2008 Dec;52(6):500–6. doi: 10.1097/FJC.0b013e31818f5739PubMedPMID:19034036
  61. Rosado EL, Bressan J, Martínez JA. Environmental Factors and Beta2‐Adrenergic Receptor Polymorphism: Influence on the Energy Expenditure and Nutritional Status of Obese Women. Lipids. 2015 May 18;50(5):459–67. doi: 10.1007/s11745-015-4012-1
  62. Macho-Azcarate T, Marti A, Calabuig J, Martinez J. Basal fat oxidation and after a peak oxygen consumption test in obese women with a β2 adrenoceptor gene polymorphism. J Nutr Biochem. 2003 May;14(5):275–9. doi: 10.1016/S0955-2863(03)00035-4
  63. Jocken JWE, Blaak EE, Schiffelers S, Arner P, van Baak MA, Saris WHM. Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation. Int J Obes. 2007 May 28;31(5):813–9. doi: 10.1038/sj.ijo.0803499
  64. Ferreira-Santos L, Martinez DG, Nicolau JC, Moreira HG, Alves MJ, Pereira AC, et al. Neurovascular control during exercise in acute coronary syndrome patients with Gln27Glu polymorphism of β2-adrenergic receptor. PLoS One. 2017;12(2):e0173061. doi: 10.1371/journal.pone.0173061PubMedPMID:28235084
  65. Macho-Azcarate T, Marti A, González A, Martinez J, Ibañez J. Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women. Int J Obes. 2002 Nov 13;26(11):1434–41. doi: 10.1038/sj.ijo.0802129
  66. Rosado EL, Bressan J, Martínez JA. Environmental Factors and Beta2‐Adrenergic Receptor Polymorphism: Influence on the Energy Expenditure and Nutritional Status of Obese Women. Lipids. 2015 May 18;50(5):459–67. doi: 10.1007/s11745-015-4012-1
  67. da Fonseca ACP, Assis IS da S, Salum KCR, Palhinha L, Abreu G de M, Zembrzuski VM, et al. Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications. Front Genet. 2024;15:1363417. doi: 10.3389/fgene.2024.1363417PubMedPMID:38841722

Last update:

No citation recorded.

Last update:

No citation recorded.