ASSOCIATION OF POLYMORPHIC VARIANTS OF NON-ALLELIC GENES ADIPOQ, MTHFR, PON1, KCNJ11, TCF7L2, ITLN1 AND PPARG WITH CLINICAL AND LABORATORY PARAMETERS AMONG OBESE PATIENTS FROM KYRGYZ REPUBLIC

DOI: https://doi.org/10.29296/24999490-2022-05-06

J.T. Isakova(1), V.N. Kipen(2), K.A. Aitbaev(1), S.B. Mukeeva(1), Akynbek kyzy Samara(1), E.M. Mirrakhimov(3)
1-Research Institute of Molecular Biology and Medicine, Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic;
2-Institute of Genetics and Cytology of The National Academy of Sciences of Belarus,
Akademicheskaya str., 27, Minsk, 220072, Republic of Belarus;
3-National Center of Cardiology and Internal Medicine, Togolok-Moldo str, 3, Bishkek, 720040, Kyrgyz Republic

Introduction. In Kyrgyzstan about 60% of the adult population suffers from lipid metabolism disorders of varying degrees. Early identification of persons at increased risk of developing obesity is of great importance, which can be achieved through the study of molecular genetic mechanisms and the identification of genetic predictors of t of disease development. Aims. to quantify the association of g.15661G>T (ADIPOQ gene), p.A222V (MTHFR gene), p.Q192R (PON1 gene), p.K23E (KCNJ11 gene), g.53341C>T (TCF7L2 gene), p.V109D (ITLN1 gene) and p.P12A (PPARG gene) polymorphic markers with clinical signs and blood indicators in obese subjects of Kyrgyz ethnicity. Material and methods. 130 patients with obesity (65 men and 65 women) along with 115 controls, including 62 men and 53 women were included. We used clinical, ancillary, biochemical and molecular tests in all subjects. PCR with restriction fragments was used to genotype polymorphic variants of interest. Statistical analysis was conducted in Microsoft Excel (Microsoft Corporation, USA) and SPSS v.20.0 (IBM, USA). Results. In patients with RR polymorphic variant of p.Q192R (PON1), BMI was on average 1.19 kg/m2 greater compared to those with QQ/QR alternative genotypes. T allele (CT/TT genotypes) of g.53341C>T (TCF7L2) genotype in obese patients was associated with 1.45 mmol/l higher fasting blood glucose; 0.49 mmol/l total cholesterol and 2.19 units of НОМА compared to subjects with СС genotype. We also found statistically significant correlations of L-alaninaminopeptidase (LAP) with p.K23E (KCNJ11) and p.P12A (PPARG) polymorphisms. Patients carrying KK genotype of p.K23E (KCNJ11) polymorphism, which is associated with higher risk of obesity in Kyrgyz (OR 2.36 (95% CI 1.11–5.03), p=0.031), LAP was 9.03 µIU/ml lower when compared to those with EE/EK genotype. Obese patients with AA genotype of p.P12A (PPARG) showed 20.1 µIU/мл higher LAP compared to PP/AP genotypes. Conclusions. Polymorphisms p.Q192R (PON1), g.53341C> T (TCF7L2), p.K23E (KCNJ11) and p.P12A (PPARG) are associated with clinical and biochemical indicators of obesity among patients of Kyrgyz nationality.
Keywords: 
obesity, gene, association, ADIPOQ, MTHFR, PON1, KCNJ11, TCF7L2, ITLN1, PPARG, Kyrgyz population, clinical and laboratory data
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