Study of the association of distribution pattern of genotypes of C/A polymorphism of COL1A1_1 collagen gene (RS1107946) with indicators of external breathing in children with bronchial asthma
DOI:
https://doi.org/10.14739/2310-1237.2019.3.189016Keywords:
polymorphism genetic, collagen, bronchial asthma, external respiratory function, childrenAbstract
Purpose. The study of the distribution patterns of allelic genes and genotypes of the C/A polymorphism of the collagen COL1A1_1 gene (rs1107946) in children with bronchial asthma, taking into account the indicators of external respiration function.
Materials and methods. Molecular-genetic study to determine the C/A polymorphism of the collagen COL1A1_1 gene (rs1107946) was conducted in 125 children from 6 to 18 years, 100 of them with bronchial asthma who were hospitalized in the Allergic Department of the Municipal Non-Profit Enterprise “City Children Hospital No 5 of Zaporizhzhia City Council” and 25 healthy children (control group). There were no differences in age and sex in the comparison groups (P > 0.05).Genotype determination was performed by polymerase chain reaction method according to the instruction (Applied Biosystems, USA) using the samples of total DNA received from whole venous blood using SNP-Screen reagents (manufactured by “Syntol”) on amplifier CFX96TM Real-Time PCR Detection Systems (“Bio-Rad laboratories, Inc.”, USA). The ventilation function of the lungs was studied by conducting a spirometric study on a computer spirograph “PULMOREM” TU U 33.1-02066769-005-2002 (Kharkiv, Ukraine). To compare the frequencies of alleles and genotypes in different groups, the non-parametric statistical method “2 × 2 Table”, the Chi-square (df = 1) was used. Medians and interquartile intervals were also calculated, the two independent groups were compared by the Mann-Whitney criterion, the χ2 criterion. Non-parametric statistics methods for the licensed software package Statistica for Windows 6.1.RU, serial number АХХR712D833214SAN5, were used to process the obtained study data.
Results. Molecular-genetic study of distribution patterns of allelic genes of the C/A polymorphism of the COL1A1_1 collagen gene (rs1107946) in patients with bronchial asthma and in practically healthy children, showed that the allele C was registered with a frequency of 69.5 % and 84.0 %, allele A – 30.5 % and 16.0 %; dominant genotype C/C – 58 % and 76 %; heterozygous genotype C/A – 23 % and 16 %; homozygous genotype A/A – 19 % and 8 %, respectively. Children with bronchial asthma with genotype A/A had significantly lower FVC values up to 2.32 (1.55; 3.29), VCmax up to 1.69 (1.40; 2.98), FEV1 up to 1.82 (1.43; 2.98), with genotype C/C – MEF75 up to 2.34 (1.87; 3.14) when compared with patients with heterozygous genotype A/C, and very low rates of FVC were recorded in 68.75 % of children with bronchial asthma with the A/A genotype against 30.77 % of patients with the A/C genotype and 36.17 % with the C/C genotype (P < 0.05).
Conclusion. Homozygous genotype A/A of C/A polymorphism of the COL1A1_1 collagen gene (rs1107946), was associated with more pronounced disorders of ventilatory function of lungs with obstructive breathing type due to impaired collagen formation in the bronchi, which may have prognostic significance both for early diagnosis and prediction of clinical course severity of this disease as well as for prevention and treatment of bronchial obstruction in patients.
References
Abaturov, O. Ye., & Rusakova, O. O. (2015). Prohnozuvannia indyvidualnoho ryzyku rozvytku bronkhialnoi obstruktsii pry hostrykh bronkhitakh u ditei rannoho viku [Prediction of the individual risk of bronchial obstruction in acute bronchitis in infants]. Zdorov'e rebenka, 1, 55-60. [in Ukrainian].
Alifanova, S. V. (2013). Faktory ryzyku rozvytku bronkhialnoi astmy u ditei [Risk factors of bronchial asthma in children]. Current issues of pharmaceutical and medical science and practice, 3, 4-7. [in Ukrainian].
Besh, L. V. (2012). Bronkhialna astma u ditei [Bronchial asthma in children]. Zdorov'e rebenka. 8, 8-20. [in Ukrainian].
Chumachenko, N. G. (2016). Rol ekolohichnykh ta henetychnykh chynnykiv u formuvanni bronkhialnoi astmy v ditei (ohliad literatury) [The role of ecological and genetic factors in the onset of asthma in children (literature review)]. Perinatologiya i pediatriya, 3, 127-133. [in Ukrainian]. https://doi.org/10.15574/PP.2016.67.127
Savenko, U. O. (2015). Henetychni, imunni i klinichni kryterii prohnozuvannia ta optymizatsiia profilaktyky alerhichnykh zakhvoriuvan u ditei (Avtoreferat dis… k. med. nauk). [Genetic, immune and clinical criteria for projection and optimization of allergic diseases prevention in children (Dissertation for the degree of candidate of medical sciences). Bogomolets National Medical University, Kyiv. [in Ukrainian].
Alimova, Yu. B., Zhelenina, L. A., Galustyan, A. N., Korostovtsev, D. S., & Ivashchenko, T. E. (2012). Geneticheskaya geterogennost' i fenotipy bronkhial'noi astmy u detei [Genetic heterogeneity and phenotypes of bronchial asthma in children]. Voprosy prakticheskoi pediatrii, 7(6), 14-18. [in Russian].
Postma, D. S, & Koppelman, G. H. (2009). Genetics of asthma: where are we and where do we go? The Proceedings of the American Thoracis Society, 6(3), 283-287. https://doi.org/10.1513/pats.200806-047RM.
Geppe, N. A. (2012). Aktualnost' problem bronkhial'noy astmy u detey [The relevance of the problem of bronchial asthma in children]. Pediatriya, 91(3), 76-82. [in Russian].
Global Initiative for Asthma. (2019). Global Strategy for Asthma Management and Prevention. Retrieved from http: //www.ginasthma.org
Papadopoulos, N. G., Arakawa, H., Carlsen, K. H., Custovic, A., Gern, J., Lemanske, R., . . . Zeiger, R. S. (2012). International consensus on (ICON) pediatric asthma. Allergy, 67(8), 976-997. https://doi.org/10.1111/j.1398-9995.2012.02865.x
Hnateiko, O. Z., & Sadova, O. M. (2009). Deiaki aspekty problemy diahnostyky bronkhialnoi astmy u ditei [Some aspects of the problem of early diagnosis of bronchial asthma in children]. Zdorov'e rebenka, 5, 118-122. [in Ukrainian].
Solyeyko, O. V., Osipenko, I. P., & Solyeyko, L. P. (2014). "Biokhimichne oblychchia" syndromu nedyferentsiiovanoi dysplazii spoluchnoi tkanyny ["Biochemical Markers" of Undifferentiated Dysplasia of Connective Tissue]. Liky Ukrainy, 1, 6-14. [in Ukrainian].
Lytvynets, L. Ya., Synoverska, O. B., Gnateyko, O. Z., & Vyshtak, N. V. (2012). Molekuliarno-henetychni osnovy i stratehiia analizu bronkhialnoi astmy v ditei [Molecular and genetic basics and strategy of bronchial asthma analysis in children]. Zdorov'e rebenka, 7, 85-89. [in Ukrainian].
Holloway, J. W., Yang, I. A., & Holgate, S. T. (2010). Genetics of allergic disease. Journal of Allergy and Clinical Immunology, 125(2), S81-S94. https://doi.org/10.1016/j.jaci.2009.10.071
Wang, F., He, X. Y., Baines, K. J., Gunawardhana, L. P., Simpson, J. L., Li, F., & Gibson, P. G. (2011). Different inflammatory phenotypes in adults and children with acute asthma. European Respiratory Journal, 38(3), 567-574. https://doi.org/10.1183/09031936.00170110
Fedortsiv, O. Ye., Vasylieva, N. A., & Voloshyn, S. B. (2014). Funktsiia zovnishnoho dykhannia u ditei z bronkhialnoiu astmoiu [Respiratory function in children with asthma]. Aktualni pytannia pediatrii, akusherstva ta hinekolohii, 1, 21-24. [inUkrainian].
Grigola, O. G. (2013). Klinichno-spirohrafichni osoblyvosti fenotypu bronkhialnoi astmy fizychnoi napruhy v ditei shkilnoho viku [Clinical and spirometrical features of phenotype of exertional bronchial asthma in school age children]. Aktualni problemy suchasnoi medytsyny, 13(3), 115-119. [in Ukrainian].
Banadyha, N. V., & Voloshyn, S. B. (2016). Rol fenotypovykh ta henotypovykhoznak u perebihu bronkhialnoi astmy u ditei [Role of phenotypic and genotypic signs of bronchial asthma in children]. Sovremennaya pediatriya, 4, 62-66. [in Ukrainian].
Ponomarova, M. S., Furman, Ye. G., Khuzina, Ye. A. Yarulina, A. M., & Zhdanovich, E. A. (2015). Semeinyi polimorfizm gena ADRB2 pri bronkhial'noi astme v detskom vozraste [Family polymorphism of ADRB2 gene in childhood bronchial asthma]. Permskii meditsinskii zhurnal, 32(5), 30-36. [in Russian].
Ivanova, L. A. (2015). Polimorfizm heniv hlutation-S-transferazy T1, M1 ta nespetsyfichna hiperspryiniatlyvist bronkhiv pry eozynofilnii bronkhialnii astmi u ditei [Gene polymorphysm of glutation-S-transferase T1, M1 and non-specific hyperresponsiveness of bronchuses under eosinophilic bronchial asthma in children]. Astma ta alerhiia, 2, 42-46. [in Ukrainian].
Klemenov, A. V. (2003). Vnekardial'nye proyavleniya nedifferentsirovannoi displazii soedinitel'noi tkani [Extracardiac manifestations of undifferentiated connective tissue dysplasia]. Klinicheskaya meditsina, 81(10), 1-6. [in Russian].
Balabolkin, I. I. (2015). Vozmozhnosti terapevticheskogo kontrolya allergicheskikh boleznei u detei na sovremennom etape [Possibilities of therapeutic control of allergic diseases in children at the modern stage]. Pediatriya, 97(4), 146-150. [in Russian].
Balabolkin, I. I., & Tyumentseva, Ye. S. (2010). Genetika atopicheskikh boleznei u detei [Genetics of atopic diseases in children]. Vestnik Rossiiskoi akademii meditsinskikh nauk, 4, 15-22. [in Russian].
Baklunov, V. V. (2006). Sistemnaya displaziya soedinitel'noi tkani - odin iz vazhnykh faktorov formirovaniya retsidiviruyushchego bronkhita u detei [Systemic dysplasia of the connective tissue - one of the most important factors in the formation of recurrent bronchitis in children]. Sovremennaya pediatriya, 4, 193-196. [in Russian].
Robinson, D. S. (2010). The role of the T cell in asthma. Journal of Allergy and Clinical Immunology, 126(6), 1081-1091. https://doi.org/10.1016/j.jaci.2010.06.025
Gibeon, D., & Chung, K. F. (2012). The investigation of severe asthma to define phenotypes. Clinical and Experimental Allergy, 42(5), 678-692. https://doi.org/10.1111/j.1365-2222.2012.03959.x
Slager, R. E., Hawkins, G. A., Li, X. N., Postma, D. S., Meyers, D. A., & Bleecker, E. R. (2012). Genetics of Asthma Susceptibility and Severity. Clinics in Chest Medicine, 33(3), 431-+. https://doi.org/10.1016/j.ccm.2012.05.005
Portelli, M., & Sayers, I. (2012). Genetic basis for personalized medicine in asthma. Expert Review of Respiratory Medicine, 6(2), 223-236. https://doi.org/10.1586/ers.12.9
Bhakta, N. R., & Woodruff, P. G. (2011). Human asthma phenotypes: from the clinic, to cytokines, and back again. Immunological Reviews, 242, 220-232. https://doi.org/10.1111/j.1600-065X.2011.01032.x
Xie, P. G., Liu, B., Zhang, L. M., Chen, R. Q., Yang, B., Dong, J. W., & Rong, L. M. (2015). Association of COL1A1 polymorphisms with osteoporosis: a meta-analysis of clinical studies. International Journal of Clinical and Experimental Medicine, 8(9), 14764-14781.
McKusick, V. A., & Amberger, J. S. (1994). The morbid anatomy of the human genome - chromosomal location of mutations causing disease. Journal of Medical Genetics, 31(4), 265-279. https://doi.org/10.1136/jmg.31.4.265
Malachkova, N. V., Yatsenko, D. A., Lyudkevich, G. P., & Shkarupa, V. N. (2019). Vinnytsia National Pirogov Memorial Medical University, Vinnytsia, Ukraine [Investigation of the value of rs1107946 polymorphism of COL1A1 gene in the development of myopia in children of the Podilia region of Ukraine]. Arkhiv oftalmolohii Ukrainy, 7(1), 35-39. [in Ukrainian]. https://doi.org/10.22141/2309-8147.7.1.2019.163004
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