FSHR gene polymorphisms affect the ovarian response to rFSH stimulation in Egyptian patients undergoing ARTs: a step toward individualized medicine Wael EL-Garf a , Sondos Salem a , Amr EL-Nouri b , Sameh Salama a , Mohammed Mohamady c , Mamdouh Bibers a , Tamer Taha a and Osama Azmy a Objective The aim of the study was to assess the potential of follicle-stimulating hormone receptor (FSHR) gene polymorphism for predicting ovarian response to FSH stimulation. Methods We retrospectively analyzed clinical data of 150 infertile women younger than 40 years who were attending the National Research Center infertility clinic, Egypt. These women were divided into two groups: group I patients (75 patients) were considered as poor ovarian responders according to the ‘Bologna criteria’ and group II patients (75 patients) were considered as good responders. Analysis of FSHR gene polymorphism at position 680 was carried out after the women were genotyped. Results Among Egyptian women, the frequency of the Asn/Asn genotype was significantly more prevalent in the poor responder group (65.3%) compared with the good responder group (24.0%) (P < 0.05); the Ser/Asn genotype was seen in 34.7% of poor responders compared with 64% of good responders and the Ser/Ser phenotype was seen only in good responders (12%). Conclusion It was found that polymorphism + 2039A > G (p.Asn680Ser) of FSHR could be suggested as a good predictor of ovarian response upon controlled FSH stimulation. Med Res J 13:61–67  c 2014 Medical Research Journal. Medical Research Journal 2014, 13:61–67 Keywords: follicle-stimulating hormone receptor, follicle-stimulating hormone stimulation, polymorphism Departments of a Reproductive Health and Family Planning Research, National Research Center, b Medical Science, National Institute of Laser Sciences, Cairo University and c Technical Support, Analysis for Life Technologies Laboratories, Cairo, Egypt Correspondence to Osama Azmy, MD, FRCOG, DFFP, Department of Reproductive Health and Family Planning Research, National Research Centre, El-Bohouth Street, Dokki, 11341 PO Box 12311, Cairo, Egypt Tel: +20 122 310 3084; fax: +20 2 37601877; e-mail: osamaazmy@yahoo.com Received 12 August 2014 accepted 15 October 2014 Introduction ollicle-stimulating hormone (FSH) plays a central role in establishing and maintaining human fertility. Circulating FSH stimulates gametogenesis and steroidogenesis in gonads by binding to its receptor [follicle-stimulating hormone receptor (FSHR)] [1]. The FSHR gene is localized on chromosome 2p21 and possesses a large number of single-nucleotide polymorphisms (SNPs). SNPs mean single-letter mutations – that is, a single-base mutation that substitutes one nucleotide for another resulting in polymorphism [2]. More than 19 million SNPs have been identified in the human genome. Most SNPs seem to have no apparent effect on gene function. However, some SNPs have a profound impact on the function of associated genes, causing significant changes in drug efficacy and drug disposition [3]. It is well known that there is individual variation in drug response; one aspect that can influence the effectiveness of therapies in patients during drug-based treatment are specific genetic var- iants [4]. SNPs have been increasingly recognized as a possible mechanism of interindividual variation in drug response [5,6]. However, for certain drugs genetic factors can account for up to 95% of interindividual variability in drug disposition and effect [7]. The idea that genetic variability between patients might influence the response to drugs was described and termed pharmacogenetics by Vogel [8]. Pharmacogenomics is the branch of pharmacol- ogy that deals with the influence of genetic variation on drug response in patients by correlating gene expression or SNPs with a drug’s efficacy or toxicity [9]. About 60–90% of the individual variation of drug response depends on pharmacogenomic factors [10]. By studying correlations between gene expression or SNPs and the efficacy or toxicity of a drug, pharmacogenomics aims to identify the inherited basis for interindividual differences in drug response and translate this to molecular diagnostics that can be used to individualize drug therapy. The ultimate goal is to provide new strategies for optimizing drug therapy [9]. FSH polymorphisms exhibit a potential for pharmacogenetic applications in selecting appropriate treatment options in conditions that require or benefit from FSH therapy [10]. Such approaches promise the advent of ‘personalized medicine’ in which drugs and drug combinations are tailored to each individual’s unique genetic makeup. SNPs in the FSHR gene have received a great deal of attention as they affect ovarian response to FSH in women undergoing assisted reproduction techni- ques (ARTs). In fact, the importance of mutations in the FSHR gene in ovarian response has been confirmed by various well-designed clinical studies [11–13] and reviewed in depth elsewhere [14–17]. The FSHR SNPs at nucleotide position 919 and 2039 in exon 10 are very common and result in the amino acid transition Thr/Ala at codon 307 and Asn/Ser at codon 680, respectively. The SNP in position 680 (Asp680Ser) in the amino acid chain has been correlated with an altered response to FSH [18]. Studies have suggested that Original article 61 2090-6242  c 2014 Medical Research Journal DOI: 10.1097/01.MJX.0000457181.82015.bd Copyright © Medical Research Journal. 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