The Association of Leptin Receptor Gene Q223R Polymorphism with Obesity in the Yakut Population

Nadezhda I. Pavlova, Alexey A. Bochurov, Vladislav A. Alekseev, Alexey V. Krylov, Lyubovy A. Sydykova, Khariton A. Kurtanov

 
For citation: Pavlova NI, Bochurov AA, Alekseev VA, Krylov AV, Sydykova LA, Kurtanov KA. The Association of Leptin Receptor Gene Q223R Polymorphism with Obesity in the Yakut Population. International Journal of Biomedicine. 2024;14(1):104-109. doi:10.21103/Article14(1)_OA16
 
Originally published March 1, 2024

Abstract: 

Background: This study aimed to compare the frequencies of alleles and genotypes of the LEPR Q223R SNP in the Yakut population in samples with normal BMI and obesity and compare the data obtained with other populations worldwide.
Methods and Results: The study included 336 DNA samples from volunteers of Yakut nationality (117 women and 219 men) without chronic diseases, whose average age was 47.4±0.06 years. All volunteers were divided into two groups: Group 1 (n=151) with normal BMI and Group 2 (n=185) with obesity. Group 2 was divided into two subgroups: Group 2A (n=156) with BMI ≥30 kg/m2 plus OA and Group 2B (n=29) with BMI ≥30 kg/m2 and without abdominal obesity.
The study of the LEPR Q223R SNP was performed using the PCR-RFLP method. The frequency of the G allele of the LEPR Q223R SNP was 79.5% in Group 1 and 82.7% in Group 2. Analysis showed a high frequency of genotype GG: 64.2% and 69.7% in Group 1 and Group 2, respectively. The frequency of the GA genotype was 30.5% in Group 1 and 25.9% in Group 2.  The frequency of alleles and genotypes does not differ in the sample of Yakuts with normal BMI and those with obesity. There are also no differences in the frequency of alleles and genotypes based on gender and the presence of abdominal obesity.
The high frequency of the G allele in the Yakut population is close to that observed in East Asian populations (86.9%). There was no statistical difference in allele frequencies in comparison with the populations of Han Chinese from Beijing, Japanese from Tokyo, and Vietnamese from Ho Chi Minh City. In European, African, American, and South Asian populations, the G allele occurs with a frequency of 43.7% to 59.2%.
Conclusion: The LEPR Q223R SNP does not affect BMI in the Yakut population. In this study, Q223R allele frequencies were like allele frequencies in East Asian populations but not in Caucasians, reflecting racial diversity in the allele distribution of this polymorphism.

Keywords: 
body mass index • LEPR gene • Q223R SNP • Yakut population
References: 
  1. Tiwari A, Balasundaram P. Public Health Considerations Regarding Obesity. 2023 Jun 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 34283488.
  2. Bender N, Allemann N, Marek D, Vollenweider P, Waeber G, Mooser V, Egger M, Bochud M. Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study. PLoS One. 2011;6(10):e26157. doi: 10.1371/journal.pone.0026157. Epub 2011 Oct 18. PMID: 22028824; PMCID: PMC3196514.
  3. Hastuti P, Zukhrufia I, Padwaswari MH, Nuraini A, Sadewa AH. Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia. Egyptian Journal of Medical Human Genetics. 2016;17(3):271-276. doi: 10.1016/j.ejmhg.2015.12.011
  4. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253. PMID: 11234459.
  5. GSR and the 1000 Genomes Project. Available from: https://www.internationalgenome.org/
  6. Ammosova EP, Klimova TM, Zakharova RN, Fedorov AI, Baltakhinova ME. [Polymorphic marker rs137100 of the LEPR gene and metabolic disorders in the indigenous population of Yakutia]. Yakut Medical Journal. 2021;74(2):5-9. doi: 10.25789/YMJ.2021.74.01. [In Russian].
  7. Asekritova AS, Borisova EP, Kylbanova ES, Maksimova NR. [Genetic aspects of metabolic syndrome in the Yakut ethnic group]. Yakut Medical Journal. 2014;46(2):32-35. [In Russian].
  8. Ievleva KD. Patterns of changes in energy metabolism and the mechanism of its genetic determination in adolescents of two ethnic groups with excess body weight. A PhD thesis. Irkutsk, 2022. [In Russian].
  9. Fan SH, Say YH. Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population. J Physiol Anthropol. 2014 Jun 20;33(1):15. doi: 10.1186/1880-6805-33-15. PMID: 24947733; PMCID: PMC4073586.
  10. Okada T, Ohzeki T, Nakagawa Y, Sugihara S, Arisaka O; Study Group of Pediatric Obesity and Its related Metabolism. Impact of leptin and leptin-receptor gene polymorphisms on serum lipids in Japanese obese children. Acta Paediatr. 2010 Aug;99(8):1213-7. doi: 10.1111/j.1651-2227.2010.01778.x. Epub 2010 Feb 23. PMID: 20222875.
  11. Marcos-Pasero H, Aguilar-Aguilar E, Colmenarejo G, Ramírez de Molina A, Reglero G, Loria-Kohen V. The Q223R Polymorphism of the Leptin Receptor Gene as a Predictor of Weight Gain in Childhood Obesity and the Identification of Possible Factors Involved. Genes (Basel). 2020 May 17;11(5):560. doi: 10.3390/genes11050560. PMID: 32429577; PMCID: PMC7288327.
  12. Sebro R, Hoffman TJ, Lange C, Rogus JJ, Risch NJ. Testing for non-random mating: evidence for ancestry-related assortative mating in the Framingham heart study. Genet Epidemiol. 2010 Nov;34(7):674-9. doi: 10.1002/gepi.20528. PMID: 20842694; PMCID: PMC3775670.
  13. Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, Auton A, Indap A, King KS, Bergmann S, Nelson MR, Stephens M, Bustamante CD. Genes mirror geography within Europe. Nature. 2008 Nov 6;456(7218):98-101. doi: 10.1038/nature07331. Epub 2008 Aug 31. Erratum in: Nature. 2008 Nov 13;456(7219):274. PMID: 18758442; PMCID: PMC2735096.
  14. 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. doi: 10.1186/s13104-020-4898-4. PMID: 31948470; PMCID: PMC6966896.
  15. Pavlova NI, Krylov AV, Alekseev VA, Bochurov AA. [Association of the Ala54Thr polymorphism of the FABP2 gene with obesity in the Yakut population]. Modern Problems of Science and Education. 2023;(2). doi:10.17513/spno.32482. [In Russian].
  16. Simcox J, Geoghegan G, Maschek JA, Bensard CL, Pasquali M, Miao R, Lee S, Jiang L, Huck I, Kershaw EE, Donato AJ, Apte U, Longo N, Rutter J, Schreiber R, Zechner R, Cox J, Villanueva CJ. Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis. Cell Metab. 2017 Sep 5;26(3):509-522.e6. doi: 10.1016/j.cmet.2017.08.006. PMID: 28877455; PMCID: PMC5658052.
  17. Sazzini M, Schiavo G, De Fanti S, Martelli PL, Casadio R, Luiselli D. Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes. Heredity (Edinb). 2014 Sep;113(3):259-67. doi: 10.1038/hdy.2014.24. Epub 2014 Mar 26. PMID: 24667833; PMCID: PMC4815638.
  18. Silvert M, Quintana-Murci L, Rotival M. Impact and Evolutionary Determinants of Neanderthal Introgression on Transcriptional and Post-Transcriptional Regulation. Am J Hum Genet. 2019 Jun 6;104(6):1241-1250. doi: 10.1016/j.ajhg.2019.04.016. Epub 2019 May 30. PMID: 31155285; PMCID: PMC6557732.
  19. Aijälä M, Malo E, Ukkola O, Bloigu R, Lehenkari P, Autio-Harmainen H, Santaniemi M, Kesäniemi YA. Long-term fructose feeding changes the expression of leptin receptors and autophagy genes in the adipose tissue and liver of male rats: a possible link to elevated triglycerides. Genes Nutr. 2013 Nov;8(6):623-35. doi: 10.1007/s12263-013-0357-3. Epub 2013 Oct 2. PMID: 24085619; PMCID: PMC3824831.
  20. Hancock AM, Witonsky DB, Gordon AS, Eshel G, Pritchard JK, Coop G, Di Rienzo A. Adaptations to climate in candidate genes for common metabolic disorders. PLoS Genet. 2008 Feb;4(2):e32. doi: 10.1371/journal.pgen.0040032. PMID: 18282109; PMCID: PMC2242814.

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Received January 19, 2024.
Accepted February 25, 2024.
©2024 International Medical Research and Development Corporation.