Patologìâ (Dec 2019)
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
Abstract
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.
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