Follicle-Stimulating Hormone Receptor Polymorphism (G−29A) Is Associated with Altered Level of Receptor Expression in Granulosa Cells

Abstract

Poor ovarian response observed in subjects with the AA genotype at position -29 of the FSHR gene is due to reduced receptor expression.

Impact of follicle-stimulating hormone receptor variants in female infertility

“…a Median values are given due to absence of normal distribution differ significantly between the controls and the patients (P= 0.502, P>0.05); moreover, there was no significant correlation of the SNP in the promoter region with baseline FSH, LH, E2, and PRL levels (P>0.05), which were consistent with the results of the studies of [34][35][36][37]. Acherekar et al [32] studied the −29 position in patients suffering from primary and secondary amenorrhea and found that the prevalence of AA genotypes at the −29 position was significantly higher in both amenorrheic groups as compared to the control group.…”

The carriers of the A/G-G/G allelic combination of the c.2039 A>G and c.-29 G>A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles

“…This observation contradicts various studies conducted on c.2039 A>G [5][6][7][8][9][10][11] but is similar to others [12][13][14][15][16][17]. In the studies focusing on c.-29 G>A polymorphism, no correlation was found with basal FSH [4,[28][29][30]; this was in line with our observation.…”

“…On the other hand, and with reference to the paper by Achrekar et al [29], patients with the A/A variant required a higher total dose of gonadotropins in order to reach significantly lower levels of estradiol on the day of hCG administration with a lower number of retrieved oocytes. The preliminary results of this study were subsequently confirmed with a demonstrated reduction in FSHR gene expression in granulosa cells [30]. By considering the association of the c.2039 A>G and c.-29 G>A polymorphisms, it has been proven that 75% of the patients with the combination A/A-A/A were poor responders, with a significant decrease in this category of FSHR expression in granulosa cells [31].…”

“…The second study [28] showed that patients carrying the diplotype with variant alleles for both the polymorphisms (G for c.2039 A>G and A for c.-29 G>A) were more likely to have a hyper-response to stimulation but, again, no correlation was observed with poor response. Considering the third study [30], conducted on an Indian population, the authors found that A/A (Asn/Asn)-G/ G and A/G (Asn/Ser)-G/G were the genetic combinations associated with the highest number of collected oocytes. Specifically, the difference between these two categories was not significant (16.4 ± 1.5 vs. 15.1 ± 1.2).…”

“…As regards the Bnew^FSHR polymorphism c.-29 G>A, few studies have been published [4,[28][29][30][31]. Specifically, Wunsch et al [4] have found no correlation of this polymorphism with ovarian reserve or ovarian response to stimulation.…”