GPR30 Gene Polymorphisms Are Associated with Gynecomastia Risk in Adolescents

Abstract

Aim: The G protein-coupled receptor, GPR30, which is a third estrogen receptor, has been shown to mediate estrogenic effects on the essential features of human breast cancer cells. The aim of this study was to evaluate the association between GPR30 single nucleotide polymorphisms and gynecomastia in males. Methods: This study included 109 male adolescents with gynecomastia and 104 controls. Follicle stimulating hormone, luteinizing hormone, total testosterone, estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and prolactin levels were measured. DNA was extracted from whole blood using a GeneJET Genomic DNA purification kit. The genotypes of the GPR30 gene (rs3808350, rs3808351 and rs11544331) were studied using a tetra-primer ARMS (amplification refractory mutation system) PCR approach. Results: The median E2 (11.80 vs. 16.86 IU/l, p < 0.001) and DHEAS levels (116.8 vs. 146.5 μg/dl, p = 0.044) were higher in the gynecomastia group. The G allele of rs3808350 and the A allele of rs3808351 were frequently observed in patients with gynecomastia. Gynecomastia was more common in patients with the GG genotype of rs3808350 and in patients with the AA genotype of rs3808351. Conclusions: Our results suggest that increased E2 levels, the G allele of rs3808350 and the A allele of rs3808351 might explain why certain adolescents are affected by gynecomastia.

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

“…The GG genotype of both the rs3808350 and rs3808351 polymorphisms and GGC haplotype increased the risk of developing leiomyoma. Our findings are consistent with those of Korkmaz et al [28] and with the SNP location, which might explain the changes in GPR30 expression described by Tian et al [19].…”

“…Chevalier et al [27] demonstrated that the GG genotype in both the rs3808350 and rs3808351 polymorphisms protected against seminoma in Caucasian males. Finally, Korkmaz et al [28] reported that the GG genotype of rs3808350, AA Statistically significant results are shown in bold genotype of rs3808351, G allele of rs3808350, and A allele of rs3808351 increased the risk of gynecomastia in a Turkish population.…”

“…Although associations between SNPs of GPR30 and several diseases, such as breast carcinoma [20], seminoma [27], and gynecomastia [28], have been investigated, this is the first study to investigate the association between leiomyoma development and GPR30 SNPs. Giess et al [20] evaluated the association between GPR30 SNPs and breast carcinoma and reported no significant differences in the allele, genotype, or haplotype frequencies of SNPs between breast carcinoma and healthy individuals, whereas SNPs of the GPR30 gene were strongly associated with lymph node involvement, tumor size, histological grade, and progesterone receptor status.…”

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.…”

Transmembrane G protein–coupled receptor 30 (GPR30) gene polymorphisms in Korean Women with Ovarian Cancer: An experimental study

“…We reviewed medical records of patients and compared the distribution of the genotype and allele frequencies of fourteen (14) GPR30 SNPs in patients with and without ovarian cancer.…”