Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing Ltd.
ISSN:
1312-773X (Online)
Issue:
2025, vol. 31, issue3
Subject Area:
Medicine
-
DOI:
10.5272/jimab.2025313.6299
Published online: 01 July 2025
Original article
J of IMAB. 2025 Jul-Sep;31(3):6299-6304
ASSOCIATION OF THE LEPTIN RECEPTOR Q223R GENE POLYMORPHISM AND FASTING PLASMA GLUCOSE LEVELS IN NORTH BULGARIAN SUBJECTS
Tihomir Rashev1
, Vladislav Nankov1, 2
, Desislava Marinova1
, Stefan Trifonov1


,
1) Department of Anatomy, Histology, Cytology and Biology, Faculty of Medicine, Medical University - Pleven, Bulgaria.
2) Scientific Research Laboratory, Medical University - Pleven, Bulgaria.
ABSTRACT:
Purpose: Obesity, diabetes, and insulin resistance are growing public health concerns, and their incidences are constantly increasing. Imbalances in whole body glucose and insulin homeostasis are also closely linked to the trend of increased obesity. A number of single nucleotide polymorphisms (SNPs) of the coding region of the leptin receptor (LEPR) gene have been described and associated with obesity measures in different ethnic groups. In Q223R polymorphism, there is a non-conservative A to G substitution at codon 223, resulting in the replacement of glutamine with arginine amino acid. This changes the binding affinity of LEPR and impairs leptin signaling. The aim of the present study was to investigate the association between the Q223R SNP and obesity related anthropometric and biochemical parameters in the North Bulgarian population.
Material/Methods. The study included 156 subjects. Body weight, body mass index and blood pressure were measured, and levels of fasting plasma glucose (FPG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL) were determined. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism.
Results. The results showed a significant association between the GG genotype of the LEPR Q223R polymorphism and elevated FPG levels. However, no association was found between LEPR genotypes and obesity status, HDL, LDL, or TC levels in North Bulgarian participants.
Conclusions. The homozygous GG genotype of the LEPR Q223R polymorphism is associated with higher fasting plasma glucose levels and may be a predisposing factor for type 2 diabetes mellitus.
Keywords: Leptin receptor, LEPR Q223R polymorphism, obesity, fasting plasma glucose,
- Download FULL TEXT /PDF 501 KB/
Please cite this article as: Rashev T, Nankov V, Marinova D, Trifonov S. Association of the leptin receptor Q223R gene polymorphism and fasting plasma glucose levels in North Bulgarian subjects. J of IMAB. 2025 Jul-Sep;31(3):6299-6304. [Crossref - 10.5272/jimab.2025313.6299]
Correspondence to: Stefan Trifonov, MD, PhD, Department of Anatomy, Histology, Cytology and Biology, Faculty of Medicine, Medical University – Pleven; 1, St. Kliment Ohridski Str., 5800 Pleven, Bulgaria; E-mail: stefantrifonov@outlook.com
REFERENCES:
1. Mohanraj J, D'Souza UJA, Fong SY, Karkada IR, Jaiprakash H. Association between leptin (G2548A) and leptin receptor (Q223R) polymorphisms with plasma leptin, BMI, stress, sleep and eating patterns among the multiethnic young Malaysian adult population from a healthcare university. Int J Environ Res Public Health. 2022 Jul;19(14):8862. [PubMed]
2. Ludwig DS. Epidemic childhood obesity: not yet the end of the beginning. Pediatrics. 2018 Mar;141(3): e20174078. [PubMed]
3. Choi YH, Fujikawa T, Lee J, Reuter A, Kim KW. Revisiting the ventral medial nucleus of the hypothalamus: the roles of SF-1 neurons in energy homeostasis. Front Neurosci. 2013 May 7; 7:71. [PubMed]
4. Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med. 2007 Jan;356(3):237-47. [PubMed]
5. Gotoda T, Manning BS, Goldstone AP, Imrie H, Evans AL, Strosberg AD, et al. Leptin receptor gene variation and obesity: lack of association in a white British male population. Hum Mol Genet. 1997 Jun;6(6):869-76. [PubMed]
6. Quinton ND, Lee AJ, Ross RJ, Eastell R, Blakemore AI. A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum Genet. 2001 Mar;108(3):233-6. [PubMed]
7. Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D, Mantzoros CS. The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab. 2001 Sep;86(9):4434-9. [PubMed]
8. Zhang Y, Hu X, Xu Q, et al. Association between LEPR Q223R polymorphism and obesity risk: A meta-analysis. PLoS One. 2013;8(11):e79556. [PubMed]
9. Constantin A, Costache G, Sima AV, Glavce CS, Vladica M, Popov DL. Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects. Biochem Biophys Res Commun. 2010 Jan 1;391(1):282-6. [PubMed]
10. Duarte SF, Francischetti EA, Genelhu VA, Cabello PH, Pimentel MM. LEPR p.Q223R, beta3-AR p.W64R and LEP c.-2548G>A gene variants in obese Brazilian subjects. Genet Mol Res. 2007 Oct 5;6(4):1035-43. [PubMed]
11. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998 Jul;15(7):539-53. [PubMed]
12. WMA. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Organ. 2001; 79(4):373-4. Epub 2003 Jul 2. [PubMed]
13. Rashev T, Marinova D, Dobrev M, Trifonov S. De novo design of a PCR-RFLP assay for detecting the leptin receptors single nucleotide polymorphism in hypothalamic nuclei. J of IMAB. 2022; 28(Suppl 1):59-62. [Crossref]
14. Hristova PM, Nankov VM, Stoikov I, Ivanov IN, Ouzunova-Raykova VV, Hitkova HY. Prevalence of genes encoding resistance to aminoglycosides and virulence factors among intestinal vancomycin-resistant enterococci. Jundishapur J Microbiol. 2022 Nov;15(9):e128003. [Crossref]
15. Constantin A, Costache G, Sima AV, Glavce CS, Vladica M, Popov DL. Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects. Biochem Biophys Res Commun. 2010 Jan 1;391(1):282-6. [PubMed]
16. Illangasekera YA, Kumarasiri PVR, Fernando DJ, Dalton CF. Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans. BMC Res Notes. 2020 Jan 16;13(1):34. [PubMed ]
17. Becer E, Mehmetçik G, Bareke H, Serakıncı N. Association of leptin receptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects. Gene. 2013 Oct 15;529(1):16-20. [Crossref]
18. Murugesan D, Arunachalam T, Ramamurthy V, Subramanian S. Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore. Indian J Hum Genet. 2010 May;16(2):72-7. [PubMed]
19. Chiu KC, Chu A, Chuang LM, Saad MF. Association of leptin receptor polymorphism with insulin resistance. Eur J Endocrinol. 2004 May;150(5):725-9. [PubMed]
20. Rosmond R, Chagnon YC, Holm G, Chagnon M, Pérusse L, Lindell K, et al. Hypertension in obesity and the leptin receptor gene locus. J Clin Endocrinol Metab. 2000 Sep; 85(9):3126-31. [PubMed]
Received: 20 November 2024
Published online: 01 July 2025
back to Online Journal