Abstract
The G-protein-coupled estrogen receptor (GPR30, 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.
Highlights
Uterine leiomyoma is the most common benign tumor originating from uterine smooth muscle cells of the myometrium [1]
There were no significant differences in median age, hemoglobin level, or body mass index (BMI) between the leiomyoma and control patients (p=0.530, p=0.183, and p>0.05, respectively)
In the allele frequency analysis, individuals with the rs3808351 GPR30 polymorphism G allele had a higher risk of developing leiomyoma than did individuals with the A allele (p=0.004) (Table 3)
Summary
Uterine leiomyoma is the most common benign tumor originating from uterine smooth muscle cells of the myometrium [1]. GPR30 protein binds estrogen, resulting in intracellular calcium mobilization and the synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein plays a role in the rapid non-genomic signaling events widely observed following the stimulation of cells and tissues with estrogen [7]. Et al.: GPR-30 gene polymorphisms and leiomyoma risk contractility in rat myometrial cells [15]. We investigated the association between GPR30 gene polymorphisms and leiomyoma for the first time. Haplotype, and allele frequencies of three GPR30 SNPs in women with leiomyoma and healthy perimenopausal women as well as within leiomyoma subgroups based on leiomyoma number and size. These comparisons were performed to determine whether GPR30 SNPs are related to the risk and characteristics of leiomyoma and to evaluate the early diagnostic potential of those SNPs
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