THE ROLE OF LEPTIN AND LEPTIN RECEPTOR GENE POLYMORPHISM IN THE OMEGA-3 POLYUNSATURATED FATTY ACIDS METABOLIC EFFECT REALIZATION IN TYPE 2 DIABETIC PATIENTS OF THE EAST UKRAINIAN POPULATION
Keywords:type 2 diabetes mellitus, leptin gene, leptin receptor gene, polymorphism, polyunsaturated fatty acids
It is known that single nucleotide polymorphisms (SNPs) in the adipokine genes can affect both the development of pathological conditions associated with obesity and the effectiveness of pharmacotherapy. Aim. To evaluate the impact of polymorphic variants for leptin gene LEP 2548G>A (rs7799039) and leptin receptor gene LEPR 223G>A (rs1137101) on the omega-3 polyunsaturated fatty acids therapeutic efficacy realization in patients with type 2 diabetes mellitus of the East Ukrainian population. A total of 61 patients with type 2 diabetes mellitus (DM) (m/f 34/27; age 53.4 ± 1.4 yrs, diabetes duration 5.3 ± 0.7 yrs; fasting blood glucose 9.1 ± 0.4 mmol/l; HbA1c 7.7 ± 0.2%) overweight or obese (body mass index 33.3 ± 0.9 kg/m2) were received in addition to standard oral hypoglycemic therapy (sulfonylurea and/or metformin) daily for 3 months the omega-3 polyunsaturated fatty acids (PUFA) (460 mg eicosapentaenoic acid + 380 mg docosahexaenoic acid). The control group consisted of 21 subjects. Clinical and biochemical parameters were assessed before and after the treatment. Genotyping by SNP LEP 2548G>A and LEPR 223G>A was performed using the polymerase chain reaction method with appropriate primers and endonucleases (HhaI and MspI). Results. It was determined that type 2 DM patients carriers of the dominant G-allele (SNP LEP 2548G>A) show greater effectiveness of omega-3 PUFA in reducing of total insulin resistance and adipose tissue insulin resistance. The association of recessive genotype (AA) by SNP LEPR 223G>A with greater efficiency of omega-3 PUFA in reducing adipose tissue insulin resistance was revealed. The studied polymorphisms of adipokine genes have an impact on the implementation of therapeutic hormonal and metabolic efficacy of omega-3 PUFA under 3-month administration in patients with type 2 DM and overweight/obesity of the East Ukrainian population. Data on polymorphic variants of the LEP and/or LEPR gene can be used within pharmacogenetics as a basis for personalized prophylaxis and therapy with a predicted effect of the pharmacological intervention.
International Diabetes Federation. Diabetes Atlas. 9th Еd, Brussels, 2019: 176 р. available at: http://www.idf.org.
Rowley WR, Bezold C, Arikan Y, et al. Popul Health Manag 2017;20: 6-12.
Giralt M, Cereijo R, Villarroya F. Handb Exp Pharmacol 2016;233: 265-282.
Sheikh A, Nasrulla A, Haq S, et al. Cureus 2017;9(7): e1435. https://doi.org/10.7759/cureus.1435.
Laxhuber KS, Morrison MJ, Chure G, et al. PLoS One 2020;15(5): e0226453. https://doi.org/10.1371/journal. pone.0226453.
Li C, Yang Y, Liu X, et al. Diabetol Metab Syndr 2020; 12(1): 97. https://doi.org/10.1186/s13098-020-00604-5.
Kasim NB, Huri HZ, Vethakkan SR, et al. Biomark Med 2016;10(4): 403-415.
Zayani N, Omezzine A, Boumaiza I, et al. J Clin Lab Anal 2017;31(6): e22148. https://doi.org/10.1002/jcla.22148.
Manriquez V, Aviles J, Salazar L, et al. Mol Diagn Ther 2018;22(1): 101-113.
Wang H, Wang C, Han W, et al. Rev Soc Bras Med Trop 2020;53: e20190388. https://doi.org/10.1590/0037-8682-0388-2019.
Aljanabi MA, Alfaqih MA, Khanfar M, et al. Biomed Rep 2021;14(5): 44. https://doi.org/10.3892/br.2021.1420.
Li Y-Y, Wang H, Yang X-X, et al. Oncotarget 2017;8(37): 61927-61934.
O'Connell TD, Mason RP, Budoff MJ, et al. Eur Heart J (Suppl) 2020;22(Suppl. J): J3-J20.
Vanden Heuvel JP. Prog Mol Biol Transl Sci 2012;108: 75-112.
Vallee Marcotte B, Cormier H, Rudkowska I, et al. J Pers Med 2017;7(4): E15.
Adams-Huet B, Devaraj S, Siegel D, Jialal I. Metab Syndr Relat Disord 2014;12(10): 503-507.
Bosviel R, Joumard-Cubizolles L, Chinetti-Gbaguidi G, et al. Free Radic Biol Med 2017;103: 146-154.