DETECTION OF RS9939609 POLYMORPHISM OF FTO GENE AND RS324011 POLYMORPHISM OF STAT6 GENE AND SEVERITY DEGREE OF BRONCHIAL ASTHMA ASSOCIATED WITH OBESITY

Alexander Fediv, Elena Melnik

Abstract


The aim of this research was to analyze the distribution of FTO and STAT6 genes polymorphism in patients with bronchial asthma (BA), associated with obesity (Ob) depending on the main disease severity degree.

Materials and methods. The study included 117 patients 18–48 years old, divided in 3 groups. The main group (bronchial asthma, associated with obesity) included 57 patients, two groups of comparison – 30 patients with the diagnosis BA and a normal body weight, and 30 patients with obesity, but without the pathology of the bronchopulmonary system.

The general genomic DNA was extracted from blood according to the standard protocol. The genetic typing was realized by the method of allele-specific amplification with the detection of results in the real time regime using TaqMan-probes, complementary to polymorphic parts of DNA. The detection of deletions in FTO and STAT 6 genes was realized by the method of polymerase chain reaction (PCR) using specific primers.

Results. In the main group, among patients with BA and Ob, carriers of Т/Т genotype were 36,84 %, Т/А – 45,61 %, А/А – 17,55 % against 40 %, 60 % and 0 % respectively in PHP group by FTO gene. Carriers of С/С genotype in the main group were 38,6 %, С/Т – 35,09 %, Т/Т – 26,31 % against 40 %, 55 % and 5 % respectively in PHP group by STAT6 gene. In the main group the light persisting BA was diagnosed in 20,0 % of cases, middle severity – in 60,0 % and severe – in 20,0 % of patients. In the group of comparison this disease severity was observed in 17,7 %, 66,5 % and 15,8 % of observations, respectively.

Conclusions. So, among patients with BA, associated with Ob with the middle and severe course of asthma the percent of heterozygous (Т/А) and mutant carriers (А/А) rs9939609 polymorphism of FTO gene is higher than at the light course. The analogous situation is observed at the study of rs324011 polymorphism of STAT6 (C2892T) gene among this category of patients. So, the determination of FTO and STAT6 genes polymorphism in patients with BA, associated with Ob, can be considered as a marker of the more severe course of asthma. 


Keywords


bronchial asthma; obesity; genes polymorphism

Full Text:

PDF

References


Fedoseev, G. B., Trofimov, V. I. (2010). "Many-sided" bronchial asthma. Russian allergological journal, 1, 40–52.

Cherkashina, I. I., Nikulin, S. Yu., Logvinenko, N. I. et. al. (2009). Clinical and genetic analysis of patients with bronchial asthma. Pulmonology, 2, 77–81.

Dixon, A. E., Holguin, F., Sood, A., Salome, C. M., Pratley, R. E. et. al. (2010). An Official American Thoracic Society Workshop Report: Obesity and Asthma. Proceedings of the American Thoracic Society, 7 (5), 325–335. doi: 10.1513/pats.200903-013st

Choquet, H., Meyre, D. (2011). Genetics of Obesity: What have we Learned? Current Genomics, 12 (3), 169–179. doi: 10.2174/138920211795677895

Asanov, A. Yu., Namazova, L. S., Pinelis, V. G., Zhurkova, N. V., Voznesenskaya, N. I. (2008). Genetic bases of bronchial asthma. Pediatric Pharmacology, 5 (4), 31–37.

Scott, H. A., Gibson, P. G., Garg, M. L., Wood, L. G. (2011). Airway inflammation is augmented by obesity and fatty acids in asthma. European Respiratory Journal, 38 (3), 594–602. doi: 10.1183/09031936.00139810

Barnes, P. J. (2013). Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. Journal of Allergy and Clinical Immunology, 131 (3), 636–645. doi: 10.1016/j.jaci.2012.12.1564

Barclay, L. (2008). Obese Patients With Asthma May Have Greater Risk for Hospitalization. Journal of Allergy and Clinical Immunology, 114, 635–648.

Boulet, L.-P. (2012). Asthma and obesity. Clinical & Experimental Allergy, 43 (1), 8–21. doi: 10.1111/j.1365-2222.2012.04040.x

Sood, A., Qualls, C., Li, R., Schuyler, M., Beckett, W. S. et. al. (2011). Lean mass predicts asthma better than fat mass among females. European Respiratory Journal, 37 (1), 65–71. doi: 10.1183/09031936.00193709

Gershon, A. S., Wang, C., Guan, J., To, T. (2010). Burden of comorbidity in individuals with asthma. Thorax, 65 (7), 612–618. doi: 10.1136/thx.2009.131078

Ivashchenko, T. E., Kelembet, N. A., Ostankova, Yu. V., Baranov, V. S. (2009). Diseases and genes of predisposition. Bronchial asthma (Genetic passport – the basis of individual and predictive medicine). Saint Petersburg: NL, 134–153.

Melen, E., Granell, R., Kogevinas, M., Strachan, D., Gonzalez, J. R., Wjst, M. et. al. (2013). Genome-wide association study of body mass index in 23 000 individuals with and without asthma. Clinical & Experimental Allergy, 43 (4), 463–474. doi: 10.1111/cea.12054

Sutherland, E. R., Goleva, E., King, T. S., Lehman, E., Stevens, A. D. et. al. (2012). Cluster Analysis of Obesity and Asthma Phenotypes. PLoS ONE, 7 (5), e36631. doi: 10.1371/journal.pone.0036631

Boulet, L.-P., Boulay, M.-E. (2011). Asthma-related comorbidities. Expert Review of Respiratory Medicine, 5 (3), 377–393. doi: 10.1586/ers.11.34

Global strategy for asthma management and prevention. National institutes of health. National Heart, Lung and Blood Institute (2014). Available at: http://www.ginasthma.org

Fischer, J., Koch, L., Emmerling, C., Vierkotten, J., Peters, T., Bruning, J. C., Ruther, U. (2009). Inactivation of the Fto gene protects from obesity. Nature, 458 (7240), 894–898. doi: 10.1038/nature07848

Zhao, X., Yang, Y., Sun, B.-F., Zhao, Y.-L., Yang, Y.-G. (2014). FTO and Obesity: Mechanisms of Association. Current Diabetes Reports, 14 (5), 486. doi: 10.1007/s11892-014-0486-0

Godava, M., Vrtel, R., Vodicka, R. (2013). Stat6 – polymorphisms, haplotypes and epistasis in relation to atopy and asthma. Biomedical Papers, 157 (2), 172–180. doi: 10.5507/bp.2013.043

Juel, C. T.-B., Ulrik, C. S. (2013). Obesity and Asthma: Impact on Severity, Asthma Control, and Response to Therapy. Respiratory Care, 58 (5), 867–873. doi: 10.4187/respcare.02202

Chung, K. F., Wenzel, S. E., Brozek, J. L., Bush, A., Castro, M., Sterk, P. J. et. al. (2013). International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal, 43 (2), 343–373. doi: 10.1183/09031936.00202013




DOI: http://dx.doi.org/10.21303/2504-5679.2017.00413

Refbacks

  • There are currently no refbacks.




Copyright (c) 2017 Alexander Fediv, Elena Melnik

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2504-5679 (Online), ISSN 2504-5660 (Print)