G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk

Abstract

The G-protein-coupled estrogen receptor , GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants' leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer' s exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population.

Oestrogen receptor alpha PvuII polymorphism and uterine fibroid incidence in Caucasian women

“…The observed differences in UF risk may be related to the occurrence of other currently not clearly identified specific genetic variants. The effect of rs934099 in ESRα gene [24] as well as [51] rs3808351 polymorphism in the gene coding G-protein-coupled oestrogen receptor (GPR30), a member of the G-protein-coupled receptor 1 family, was recently proven to be associated with UF risk occurrence and a number of tumours [51]. However, more data are necessary to assess the role of these genetic variants in UF development.…”

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER

“…Applying "reverse translational medicine" we should rethink our therapeutic approaches when using these drugs which also suggest possible new therapeutic indications such as for the treatment of bleeding in hereditary heamorrhagic telangiectasia [182] and possibilities for future drug development. Medical genetics studies have found that genetic polymorphisms of GPER are associated with changes in cell function [183] or disease susceptibility for dyslipidemia [73], arterial hypertension [108], seminoma [184], gastric cancer [185], breast cancer [186], leiomyoma [187] and gynecomastia in adolescents [188] providing us with new opportunities for personalized medicine, theranostics, and thereby improving treatment and prevention. Continued clinical research is required to increase our understanding of estrogen receptors and the clinically approved drugs targeting them and how these drugs mediate therapeutic benefits and unwanted side effects in patients, which ultimately will improve patient safety and survival.…”

Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction

“…Given their most recent discovery relative to ERα and ERβ, CVD-related GPER polymorphisms have not been thoroughly investigated although associations were already demonstrated to idiopathic scoliosis [ 155 ], the risk for seminoma [ 156 ] and uterine leiomyoma [ 157 ] and more recently, with risk and development of hypertension [ 158 ]. Moreover, a hypofunctional GPER variant P16L has recently been identified and associated with increased LDL-C in plasma, which may pose an additional risk of atherosclerosis [ 93 ].…”