Genetic analysis of the follicle stimulating hormone receptor gene in women with polycystic ovary syndrome

Abstract

This study was designed to assess the relationship between mutations in the FSH receptor (FSHr) gene and polycystic ovary syndrome (PCOS) in Italian women. The study population included 50 patients with PCOS and 50 age- and body mass index (BMI)-matched controls. A complete anthropometrical, hormonal and pelvic ultrasonographic evaluation was performed in all subjects. Genomic DNA was extracted from peripheral lymphocytes and then each exon of the FSHr gene was amplified by PCR. The mutation identified was cloned and the functional properties were studied after transient expression in COS-7 cells. Direct sequencing of exons 1-10 of the FSHr gene revealed the presence of a heterozygous AAT/ATT mutation affecting the isoleucine residue at position 411, which was replaced by an asparagine, in the second transmembrane segment (I411N). This mutation was only found in one woman with PCOS and not in her parents. This mutation was not present in 50 age and BMI controls and in another 150 women not affected by PCOS. The functional study after transient expression in COS-7 cells revealed that this I411N had similar functional characteristics with respect to the wild type FSHr (wtFSHr). Genetic analyses of polymorphisms in the human FSHr gene were also performed. All 50 women with PCOS harbored the A307T polymorphic variant, 56% harbored N680S, 30% S680S and 14% N680N polymorphisms. In conclusion, the present study demonstrates that mutations of the FSHr gene are rare in Italian women. The only mutation that we found does not appear to have any pathophysiological significance in PCOS.

Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome

“…The distribution patterns of the two alleles ("Ala" and "Thr") were similar in both groups. Moreover, in our study, distribution of the cases with N680S (45%), S680S (25%) and N680N (13%) was found to be similar to findings of Orio et al Mutations of the FSHR were found to be rare in Italian women and the only mutation found did not appear to have any pathophysiological significance in PCOS [10]. We found that these common polymorphisms did not seem to play a role in development of PCOS in adolescent girls (P> 0.05).…”

“…Two known polymorphisms, Thr307Ala and Ser680Asn of FSHR gene showed similar distributions of the allelic variations and protein isoforms in PCOS and control subjects in Chinese Singapore [11] and Caucasian women [48]. 50 Italian women with PCOS harbored the A307T polymorphic variant, 56% harbored N680S, 30% S680S and 14% N680N polymorphisms [10]. In our study, the percentages of 680Ser carriers (Ser/Asn + Ser/Ser) are nearly the same in cases (70%) and controls (72%).…”

“…As a result, amino acid alteration related to the corresponding SNPs might affect the post-translational modifications of the FSHR protein, hence the function of the receptor including FSH efficacy [8]. A few genetic studies have examined the association between FSHR gene polymorphisms and PCOS [9][10][11].…”

Study on Follicle Stimulating Hormone Receptor Gene Polymorphisms in South Indian Women With Polycystic Ovarian Syndrome

“…In the present study we did not found any significant difference in frequency of rs1394205 polymorphism between PCOS and controls in contrast to earlier studies reported on Indonesian and German women undergoing ovarian hyperstimulation (Wunsch et al, 2005) and in women with amenorrhea in Indian population (Achrekar et al, 2010). Frequency of FSHR gene exon 10 polymorphisms rs6165 and rs6166 did not differed significantly with their ethnic controls and the results are similar to the previously reported studies based Han Chinese from Singapore (Tong et al, 2001) and Shanghai (Du et al, 2010), Japanese (Sudo et al, 2002), Dutch (Laven et al, 2003), Italian (Orio et al, 2006) Turkish (Unsal et al, 2009) and Caucasian (Valkenburg et al, 2009). The only significant association between PCOS and FSHR rs6166 (G/G) genotype was found in Korean women PCOS (Gu et al, 2010).…”

Mutations and polymorphisms in FSH receptor: functional implications in human reproduction

“…A mutation at Ile 411 Asn position was detected in women with polycystic ovary syndrome (PCOS; Orio et al 2006). On the other hand, the mutations at Pro 587 His and Ala…”