Pvuii (Rs2234693) Polymorphism of the Estrogen Receptor Alpha Gene in Women From Sumy Oblast, Ukraine, With Endometrial Hyperplastic Process

Abstract

Introduction. The endometrial hyperplastic process is an estrogen-dependent benign condition of the uterus, which is frequently a cause of infertility, ovarian-menstrual cycle disorders, and malignant transformation into uterine cancer. The effect of estrogen on the endometrium is realized through the estrogen receptor alpha. It is manifested by a whole range of biological changes, including cell reproduction and growth, tissue development, etc. Estrogen receptor alpha is encoded by the ESR1 gene, which is located on chromosome 6q25 and has eight exons and seven introns. Today, about 9,000 polymorphisms of the ESR1 gene have been described, some of which are associated with gene activity changes. Such functional polymorphisms include the PvuII polymorphism (rs2234693), which occurs due to the substitution of thymine (T) for cytosine (C) in the first intron of the gene. Objective. The purpose of this study was to assess the frequency of allelic variants of the estrogen receptor alpha gene for the PvuII polymorphism in patients with endometrial hyperplastic process living in the Sumy Oblast of Ukraine and to study its relationship with the histological variant of endometrial hyperplastic process, anthropometric parameters, age categories, medical history, and concomitant diseases. Materials and Methods. Genomic DNA was isolated from blood samples of 95 women with endometrial hyperplastic processes and 80 healthy women. The rs2234693 polymorphism was studied using a polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). The data were processed and statistically analyzed with Microsoft Excel and SPSS Statistics 29.0 for Windows software package. Descriptive statistics, Student's test, ANOVA method, and Pearson's chi-squared test were used in this study. Results with P < 0.05 were considered statistically significant. Results. The distribution of genotype variants for the PvuII polymorphism of the ESR1 gene in women with endometrial hyperplastic process was: homozygotes for the major allele (T/T) – 31.6%, heterozygotes (T/C) – 49.5%, homozygotes for the minor allele (C/C) – 18.9%; in the control group, these values were 30%, 52.5%, and 17.5%, respectively. There was no difference in the distribution of genotypes in patients with endometrial hyperplastic processes and healthy women (χ2 = 0.163, P = 0.922). No associations were found between the PvuII polymorphism and the histological variant of endometrial hyperplastic processes (χ2 = 4.14, P = 0.387), anthropometric parameters (P > 0.05), age (χ2 = 2.98, P = 0.560), medical history (P > 0.05), or concomitant genital and extragenital conditions (P > 0.05). Conclusions. There was no difference in the distribution of T/T, T/C, and C/C genotypes for the PvuII polymorphism in the estrogen receptor alpha gene between patients with endometrial hyperplastic process and the control group. There was no correlation between the genotype variant for the studied polymorphism and the histological variant of the endometrial hyperplastic process, anthropometric parameters, age, medical history, concomitant genital and extragenital conditions in patients of the Sumy Oblast, Ukraine.