Polymorphism of genes controlling phase I and II detoxification in phenol-exposed women with spontaneous miscarriage diagnosis

Abstract

The environmental issues in contemporary megapolis require studying of multiple candidate genes that may contribute to occurrence of reproductive disorders. Exogenous phenol compounds are contaminants that produce negative effects upon female reproductive system. Detoxification genes from CYP450 and GSTs family belong to the I and II detoxification phases of xenobiotics including phenols. Our goal was to examine some features of polymorphism in I and II phase detoxication genes in women with diagnosed miscarriage who were subjected to excessive phenol exposure. The test group consisted of 37 women who had miscarriage; the reference group included 41 conditionally healthy women. All the examined women lived under airborn exposure to phenol (an average of 1.0 daily minimal acceptable concentration). The following parameters were examined in both groups: phenol contents in blood were detected with capillary gas chromatography; polymorphisms of CYP1A1 rs1048943 Ile462Val, CYP1A1_3 rs4646421 C6310T, GSTA4 rs3756980 T/C, GSTP1 rs1695 Ile105Val, GSTP1 rs1138272, and Ala114Val genes were revealed with polymerase chain reaction. There were significant discrepancies between the examined groups, both for phenol contents in blood, compared to upper standardized limits (p 0.05). The examined gene polymorphisms fit the Hardy–Weinberg rule. Statistical analysis in multiplicative inheritance model allowed us to show that A allele in CYP1A1 rs1048943 Ile462Val gene, and A allele in GSTP1 rs1695 Ile105Val gene could be the factors associated with probable miscarriage risk in case of excessive contamination of biological media with exogenous estrogens (e.g., phenol). The examined gene polymorphisms may be suggested as marker genes for early prediction of miscarriage risk, when excessive contents of exogenous estrogen imitator (phenol) are present in biological media.