Bronchopulmonary dysplasia in children in terms of genetic variability of the vitamin D receptor

Background. In addition to the main function of regulating calcium-phosphorus metabolism, vitamin D (VD) and its receptor (VDR) have an indirect effect on more than 300 genes that affect the cell cycle, immunity and metabolism. Of more than 30 known single nucleotide sequences, ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), and Cdx2 (rs11568820) are the most studied and have phenotypic effects on a number of diseases. Objective. Determination of the effect of the VDR gene FOK1 polymorphism on the course and outcomes of bronchopulmonary dysplasia (BPD) in children. Methods. The main group in the study consisted of 80 patients with a diagnosis of bronchopulmonary dysplasia (BPD). The control group consisted of 93 preterm infants without BPD. All patients of the main group were examined and received treatment in accordance with the standard of medical care for this disease. To perform molecular genetic analysis, total DNA was isolated from whole blood. Genotyping of polymorphic markers of the studied genes was carried out using polymerase chain reaction (PCR) and analysis of restriction fragment length polymorphism (RFLP analysis). Statistical analysis was carried out by methods of variation statistics. Results. The association of the VDR gene FOK1 polymorphism with the implementation of BPD in children has been proven. According to statistical analysis, the F/F genotype predisposes to the development of the disease (х2=7.133; p=0.008, df=1, OR=2.811, CI: 1.3006.077). The evaluation of the effect of genotypes of the VDR gene FOK1 polymorphism on the outcomes of BPD, the severity and the implementation of broncho-obstructive syndrome in BPD exacerbation, the nature of the airway microbiota and the duration of IGCS use did not reveal statistically significant differences. At the same time, a comparative analysis of the data showed that heterozygous carriers of the F/f genotype of the VDR gene FOK1 polymorphic marker significantly more often had severe lesions of the central nervous system - CNS (x2=7.619; p<0.05, p=0.006, df=1, odds ratio [OR]=9,000, confidence interval [CI]: 1.638-49.447). Analysis of the data obtained revealed a significant relationship between the heterozygous F/f genotype of the VDR gene FOK1 polymorphic marker with the incidence of acute respiratory viral infections (ARVI) (x2=3.889; p=0.049, df=2), as well as with the appearance of the first episodes of ARVI in children up to 1-year old (x2=7.347; p<0.05, p=0.020). Conclusion. The results of the study proved that the homozygous F/F genotype is predisposing to the formation of BPD in infants. The heterozygous F/f genotype of the VDR gene FOK1 polymorphic locus is associated with vascular lesions of the central nervous system, frequent episodes and early onset of viral infections, accompanied by a severe form of obstructive syndrome in children with BPD.

bronchopulmonary dysplasia, vitamin D receptor, FOK1 polymorphism