Variability study of immune status modified by polymorphic genetic profile in women with pregnancy loss under hydroxybenzene exposure

Abstract

The study was performed in Perm, an industrially developed Russian city where hydroxybenzene concentrations are excessive due to dust and gaseous emissions from non-ferrous metallurgic plants. Their concentrations exceed average daily and single maximally permissible amounts. Hydroxybenzene and its derivatives are hormone-like substances, thus being hazardous to female reproductive system. The goal of our study was to analyze variability of immune state influenced by polymorphic genetic profile of women with pregnancy loss under hydroxybenzene exposure. Chemical analysis of ambient air quality was performed according to MG 4.1.617-96 regulations. Biological samples were taken from 129 women with reproductive disorders at their fertile age during the five-year observation period. Hydroxybenzene contents in blood were detected with gas chromatography with inductively coupled plasma. The test group 1 included women with reproductive disorders and phenol contents in blood exceeding the reference level ( 0.016 mg/cm3 ). Test group 2 consisted of women with reproductive disorders and phenol contents in blood within standard ranges. The control group 1 consisted of conditionally healthy women with phenol contents in their blood being higher than 0.016 mg/cm3 . Control group 2 included conditionally healthy women with phenol contents in their blood corresponding to the standard values. Serotonin content in blood serum considered catecholamine regulation marker was estimated with ELISA technique; phenol-specific IgG contents were measured by means of modified competitive ELISA method. PCR technique was used for detection of ACTN3 rs1815739 gene polymorphism associated with catecholamine metabolism. We found that a half of the total study group were exposed to phenol and cresols at concentrations 1.0 MPC average daily and single maximal dose. Incidence of endometriosis among them tended to increase over the examined 5-year periodL this disorder is known to contribute to pregnancy loss. Chemical analysis of blood allowed us to reveal phenol contamination in all the women to varying degrees. Regression analysis allowed to reveal a significant dependence between phenol contents in blood and phenol-specific IgG, as well as significant correlation between blood serotonin contents and cresols concentrations (p 0.05). Kruskal–Wallis test revealed significant intergroup differences by serotonin levels. There were significant differences between the test groups 1 and 2 by serotonin contents (at p 0.0083 with Bonferroni correction). Frequencies of ACTN3 rs1815739 genotypes, using a multiplicative model, allowed us to assign T allele to the factors contributing to risk of reproductive losses induced by biological media contaminated with phenol in excess. Cross-classification analysis revealed a causal relationship between serotonin contents and ACTN3 rs1815739 genotype.