Study of association of the polymorphism rs1799883 of the FABP2 gene in children with bronchial asthma associated with obesity

Introduction. Currently, there is a separate phenotype “bronchial asthma – obesity”, manifested by a more severe course of the disease, low rates of achieving asthma control, resistance to basic therapy. Asthma, like obesity, is recognized as a classic example of multifactorial diseases, which are based on a rather complex gene network. The active search for genetic markers characterizing individual characteristics of human metabolism continues. Of particular interest are the genes involved in the regulation of fat and carbohydrate metabolism.

Aim. Analysis of associations of polymorphic loci Ala54Thr (G163A) of the FABP2 gene with bronchial asthma of varying severity and control of asthma in children.

Materials and methods. 161 children with bronchial asthma in remission were examined by a continuous sampling method, of which 59 patients with obesity of 1-3 degrees without concomitant endocrine pathology. The examination included general clinical, functional, and instrumental methods. The level of asthma control was determined according to the GINA criteria (2018). The biochemical study was carried out on an automatic analyzer SAPPHIRE 400 (Japan). The study of gene polymorphisms was carried out by real-time polymerase chain reaction using sets of “Metabolism” (Research and Production Company “Litekh”, Moscow) on the CFX-96 Biorat device (USA).

Results. We have not identified associations of the presence of polymorphic loci of the FABP2 gene with obesity. It was determined that in children with bronchial asthma, the frequency of carrying the homozygous genotype Thr/Thr and the minor allele Thr increased by 1.5 times compared to the control group (OR 9.043; 95%CI [2,093–39,073], p=0.0011 and OR 2.946; 95%CI [1,698‒5,111], p=0.001, respectively), and in children with bronchial asthma with and without asthma control, the carriage of the homozygous Thr/Thr genotype and the rare A allele increased the risk of uncontrolled bronchial asthma (OR 2.42; 95%CI [1.23‒4.79], p=0.03 and OR 1.75; 95%CI [1,119‒2,736], p=0.01), the frequency of the homozygous Ala/Ala genotype and the frequent Ala allele was detected 1.5 times more often in children with bronchial asthma associated with obesity (OR 2.176; 95%CI [1.001‒4.727], p=0.0008 and OR 2.378; 95%CI [1.495‒3.780], p=0.0002, respectively).

Conclusion. Although we have not identified associations of the presence of polymorphic loci of the FABP2 gene with obesity, it has been shown that children with Ala54Thr+Thr54Тhr genotypes have significantly higher glucose levels (4.9±0.06 mmol/L compared with carriers of the Ala54Ala genotype 4.0±0.06 mmol/L, p<0.001), cholesterol (4.8±0.4 mmol/L compared with carriers of the Ala54Ala genotype 3.93±0.1 mmol/L, p<0.05) and low density lipoproteins (2.55±0.09 mmol/L compared with carriers of the Ala54Ala genotype 2.26±0.1 mmol/L, p<0.05). There is an obvious need for further investigation of the effect of gene polymorphism on the indicators of carbohydrate and lipid metabolism, depending on the nature of diets. These issues require further study as part of the search for probable cause-and-effect relationships and the creation of personalized programs depending on polymorphic gene variants.

1. Baruwa P., Sarmah K.R. Obesity and asthma. Lung India 2013; 30(1):38–46. https://doi.org/10.4103/0970-2113.106132

2. Kosenkova T.V., Novikova V.P. [Bronchial asthma and obesity in children. Mechanisms of interrelation]. Medicine: theory and practice 2019; 4(1):62‒83 (in Russian). https://www.elibrary.ru/buhtor

3. Uksumenko A.A., Antonyuk M.V. [Pathogenetic aspects of the phenotype of bronchial asthma associated with obesity]. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration. 2019; (71):112–119 (in Russian). https://doi.org/10.12737/article_5c89ac3a1c1ac3.25721118

4. Irani C., Adib S., Halaby G, Sibai A. Obesity/overweight and asthma control in LEBANESE adults: a cross-sectional study. BMC Public Health 2019; 19(1):769. https://doi.org/10.1186/s12889-019-7116-3

5. Yacheykina N.A., Alimova I.L, Plutenko E.V. [Features of the course of bronchial asthma in obese children]. Vestnik of Smolensk State Medical Academy 2021; 20(2):188‒195 (in Russian). https://doi.org/10.37903/vsgma.2021.2.26

6. Mineev V.N., Lalaeva T.M., Vasilyeva T.S., Trofimov V.I. [Phenotype of bronchial asthma with obesity]. Pulmonologiya 2012; (2):102–107 (in Russian). https://doi.org/10.18093/0869-0189-2012-0-2-102-107

7. Novik G.A., Khaleva E.G., Makarova S.G., Zhdanova M.V. [Asthma and obesity in children: what do we know?]. Bulletin of Siberian Medicine 2019; 18(3):183‒191 (in Russian). https://doi.org/10.20538/1682-0363-2019-3-183-191

8. Soloveva I.A., Sobko E.A., Demko I.V., Kraposhina A.Y., Gordeeva N.V., Loktionova M.M. [Asthma and obesity]. Terapevticheskii arkhiv 2017; 89(3):116‒120 (in Russian). https://doi.org/10.17116/terarkh2017893116-120

9. Fomina D.S., Goryachkina L.A., Alekseeva Yu.G., Bobrikova E.N. [Bronchial asthma and obesity: search for therapeutic models]. Pulmonologiya 2014; (6):94‒102 (in Russian). https://doi.org/10.18093/0869-0189-2014-0-6-94-102

10. Chichkova N.V., Gasparyan A.A., Gitel E.P., Serova N.S., Fomin V.V. Asthma in overweight and obese patients: assessment of adipokine profile with different fractions of adipose tissue. Prakticheskaya pulmonologiya 2019; (3):4‒9 (in Russian). https://www.elibrary.ru/tshaix

11. Kasteleyn M.J., Bonten T.N., de Mutsert R., Thijs W., Hiemstra P.S., le Cessie S., Rosendaal F.R., Chavannes N.H., Taube C. Pulmonary function, exhaled nitric oxide and symptoms in asthma patients with obesity: a cross-sectional study. Respir. Res. 2017; 18(1):205. https://doi.org/10.1186/s12931-017-0684-9

12. Hallstrand T.S., Fisher M.E., Wurfel M.M., Afari N., Buchwald D., Goldberg J. Genetic pleiotropy between asthma and obesity in a community based sample of twins. J. Allergy Clin. Immunol. 2005; 116(6):1235–1241. https://doi.org/10.1016/j.jaci.2005.09.016

13. Shartanova N.V., Surovenko T.N., Glushkova Ye.F. [Bronchial asthma combined with obesity: modern understanding]. Effektivnaya farmakoterapiya 2015; (48):40–49 (in Russian). https://www.elibrary.ru/vilwbv

14. Sentsova T.B., Chernyak O.O., Vorozhko I.V., Gapparova K.M., Grigoryan O.N., Chekhonina Yu.G., Churicheva A.M. [Genetic predictors of the effectiveness of the standard low-calorie diet in obese patients]. Obesity and metabolism 2016; 13(3):45‒48 (in Russian). https://doi.org/10.14341/OMET2016345-48

15. Kirillova О.О. [Modern concept of gene polymorphisms, which regulate lipid metabolism]. Problems of Nutrition 2012; 81(4):48‒52 (in Russian). https://www.elibrary.ru/pjqtob

16. Leo´nska-Duniec A., Katarzyna S., Ahmetov I.I., Pickering C., Massidda M., Buryta M., Mastalerz A., Maculewicz E. FABP2 Ala54Thr Polymorphism and Post-Training Changes of Body Composition and Biochemical Parameters in Caucasian Women. Genes 2021; 12(7):954. https://doi.org/10.3390/genes12070954

17. Chaaba R., Bouaziz A., Ben Amor A., Mnif W., Hammami M., Mehri S. Fatty Acid Profile and Genetic Variants of Proteins Involved in Fatty Acid Metabolism Could Be Considered as Disease Predictor. Diagnostics (Basel) 2023; 13(5):979. https://doi.org/10.3390/diagnostics13050979

18. Shabana, Hasnain S. The fatty acid binding protein 2 (FABP2) polymorphism Ala54Thr and obesity in Pakistan: A population based study and a systematic meta-analysis. Gene 2015; 574(1):106–111. https://doi.org/10.1016/j.gene.2015.07.087

19. Abbas S., Raza S.T., Chandra A., Rizvi S., Ahmed F., Eba A., Mahdi F. Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population. Ann. Hum. Biol. 2015; 42(5):461– 469. https://doi.org/10.3109/03014460.2014.968206

20. Valeeva F.V., Khasanova K.B., Valeeva E.V., Kiseleva T.A., Sozinova E.A., Akhmetov I.I. [Association of rs1799883 polymorphism of the FABP2 gene with various disorders of carbohydrate metabolism in residents of the republic of Tatarstan]. Meditsinskiy al'manakh 2018; (6):118‒122 (in Russian). https://doi.org/10.21145/2499-9954-2018-6-116-120

21. Di Filippo P., Scaparrotta A., Rapino D., de Giorgis T., PetrosinoI., Attanasi M., Di Pillo S., Chiarelli F., Mohn A. Insulin resistance and lung function in obese asthmatic pre-pubertal children. J. Pediatr. Endocrinol. Metab. 2018; 31(1):45–51. https://doi.org/10.1515/jpem-2017-0182

22. Borodina S.V., Gapparova K.M., Zainudinov Z.M., Grigorian O.N. [Genetic predictors of obesity development]. Obesity and metabolism 2016; 13(2):7‒13. (in Russian). https://doi.org/10.14341/OMET201627-13