Gene polymorphism of the xenobiotic biotransformation system and the intrauterine fetal growth retardation in female workers of industrial enterprises

Abstract

Intrauterine growth retardation is recognized as one of the leading causes of incidence and mortality in infancy and early childhood in all the countries of the world. The causes and mechanisms of development of this process are decisive when choosing the tactics of nursing such children. Of particular importance is the understanding of the functioning of the mother-placenta-fetus system, in particular the mechanisms of suppression of the detoxification function of the placenta in connection with the polymorphisms of the genes of the I and II phases of the xenobiotic biotransformation system. The aim of the study was to determine the relationship between the polymorphism of the genes of the I and II phases of the xenobiotic biotransformation system with the intrauterine fetal growth retardation in women living in the South of the Kemerovo region and working under harmful labor conditions. A survey of 39 women of reproductive age living in the territory of Novokuznetsk was carried out, 20 of them worked at various enterprises of the city. The study group included 14 women who gave birth to children with intrauterine growth retardation of varying severity. The comparison group (control) consisted of 25 women. They did not have spontaneous miscarriages and they carried a child without the intrauterine growth retardation. The work investigated the frequency of occurrence of polymorphisms of genes of the xenobiotic biotransformation system - CYP1A2*1F, GSTM1 (they determine the activity of detoxification enzymes), as well as their combinations - in a group of working women and housewives who gave birth to children with intrauterine growth retardation. The forms of genes associated with the intrauterine fetal growth retardation, as well as genes associated with the resistance to this pathology, were identified. Combinations of gene forms of different phases of the xenobiotic biotransformation and their relationship with intrauterine fetal growth retardation were shown. There were no statistically reliable differences between various cohorts of women. A positive association of a high risk of the intrauterine fetal growth retardation in women with A/A CYP1A2*1F genotype and deletion polymorphism of the GSTM1 "-" gene has been shown. The heterozygous form of the C/A CYP1A2*1F gene polymorphism is statistically reliably associated with the resistance to this pathology, as well as the normally functioning GSTM1 "+" gene. Genotype A/A CYP1A2*1F in the combination with the deletion polymorphism of GSTM1 "-" gene is statistically reliably associated with intrauterine fetal growth retardation, and C/A CYP1A2*1F genotype in the combination with normally functioning GSTM1 "+" gene is associated with a low risk of the intrauterine fetal growth retardation. Comparative analysis of the relationship of the studied forms of genes of the xenobiotic biotransformation system with the intrauterine fetal growth retardation in the groups of female workers and housewives did not show statistically reliable differences.