Assessment of FSHR, AMH, and AMHRII variants in women with polycystic ovary syndrome.
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SUBMITTER: Czeczuga-Semeniuk E
PROVIDER: S-EPMC4371821 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSingle-nucleotide polymorphisms (SNPs) in the follicle stimulating hormone receptor (FSHR) gene are associated with PCOS. However, their relationship to the polycystic ovary (PCO) morphology remains unknown. This study aimed to investigate whether PCOS related SNPs in the FSHR gene are associated with PCO in women with PCOS.MethodsPatients were grouped into PCO (n = 384) and non-PCO (n = 63) groups. Genomic genotypes were profiled using Affymetrix human genome SNP chip 6. Two polymorphisms (rs2268361 and rs2349415) of FSHR were analyzed using a statistical approach.ResultsSignificant differences were found in the allele distributions of the GG genotype of rs2268361 between the PCO and non-PCO groups (27.6% GG, 53.4% GA, and 19.0% AA versus 33.3% GG, 36.5% GA, and 30.2% AA), while no significant differences were found in the allele distributions of the GG genotype of rs2349415. When rs2268361 was considered, there were statistically significant differences of serum follicle stimulating hormone, estradiol, and sex hormone binding globulin between genotypes in the PCO group. In case of the rs2349415 SNP, only serum sex hormone binding globulin was statistically different between genotypes in the PCO group.ConclusionsFunctional variants in FSHR gene may contribute to PCO susceptibility in women with PCOS.
| S-EPMC4529894 | biostudies-literature
Project description:PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder disease among women in reproductive-age. Since follicle stimulating hormone (FSH) exerts important biological functions, the association between PCOS and FSH receptor (FSHR) polymorphisms attracts wide attention. The aim of this study was to evaluate whether polymorphisms of FSHR at 307 and 680 codons are associated with PCOS patients in China. METHODS: Patients with PCOS (n = 215) and controls (n = 205) were recruited from Shanxi Province in north China. They are Han ethnics. Genomic DNA was isolated from the venous blood. The Ala307Thr and Ser680Asn polymorphisms of FSHR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. RESULTS: The distributions of genotype and allele of Ala307Thr and Ser680Asn polymorphisms of FSHR were not statistically different between the PCOS patients and the controls. Analysis of the frequency of FSHR polymorphisms showed no statistical difference among the PCOS patients with different obesity standards. Although there were no statistical differences in the most of the endocrine parameters including LH, LH/FSH, E2, P and T as well as the clinical pregnancy rate, there were significant differences in the levels of FSH and PRL among PCOS patients carrying different genotypes of Ala307Thr and Ser680Asn polymorphisms. CONCLUSION: The Ala307Thr and Ser680Asn polymorphisms of FSHR are not associated with PCOS in Han ethnic Chinese women in north China. The FSHR polymorphisms was related to the levels of FSH and PRL but not other PCOS-associated endocrine hormones as well as clinical pregnancy rate in PCOS patients of Han Chinese ethnical population.
| S-EPMC3947065 | biostudies-literature
Project description:ContextAnti-Müllerian hormone (AMH) reduces aromatase activity and sensitivity of follicles to FSH stimulation. Therefore, elevated serum AMH may indicate a higher threshold for response to ovulation induction in women with polycystic ovary syndrome (PCOS).ObjectiveThis study sought to determine the association between AMH levels and ovulatory response to treatment among the women enrolled into the Pregnancy in PCOS II (PPCOS II) trial.Design and settingThis was a secondary analysis of data from a randomized clinical trial in academic health centers throughout the United States Participants: A total of 748 women age 18-40 years, with PCOS and measured AMH levels at baseline, were included in this study.Main outcome measuresCouples were followed for up to five treatment cycles to determine ovulation (midluteal serum progesterone > 5 ng/mL) and the dose required to achieve ovulation.ResultsA lower mean AMH and AMH per follicle was observed among women who ovulated compared with women who never achieved ovulation during the study (geometric mean AMH, 5.54 vs 7.35 ng/mL; P = .0001; geometric mean AMH per follicle, 0.14 vs 0.18; P = .01) after adjustment for age, body mass index, T, and insulin level. As AMH levels increased, the dose of ovulation induction medication needed to achieve ovulation also increased. No associations were observed between antral follicle count and ovulation.ConclusionsThese results suggest that high serum AMH is associated with a reduced response to ovulation induction among women with PCOS. Women with higher AMH levels may require higher doses of medication to achieve ovulation.
| S-EPMC5010565 | biostudies-literature
Project description:BACKGROUND:Pathogenic variants of follicle-stimulating hormone receptor (FSHR) are known to cause amenorrhea and infertility in women. However, only a limited number of pathogenic FSHR variants have been reported, and few reports described detailed characteristics of patients with pathogenic FSHR variants. METHODS:The affected siblings and both parents were subjected to whole-genome exon sequencing. Transient transfection of HEK 293T cells was performed with constructed vectors. The cellular localization of the FSHR protein was evaluated using confocal microscopy, and cyclic adenosine monophosphate (cAMP) production was detected with a cAMP ELISA kit. RESULTS:A Chinese family with two siblings carrying compound heterozygous pathogenic variants of FSHR: c.182T>A (p.Ile61Asn) and c.2062C>A (p.Pro688Thr). Both siblings had amenorrhea, infertility, and resistance to gonadotropin (Gn) stimulation but showed high anti-Müllerian hormone levels and early antral follicles. Molecular dynamics simulations of the FSHR variants revealed significant changes in structural characteristics and electrostatic potential. In vitro analysis indicated that the p.Ile61Asn variant lacked cell surface localization and completely abolished the cAMP second messenger response. The p.Pro688Thr variant retained cell surface localization but caused decreased FSH-induced cAMP production. CONCLUSION:We found two novel pathogenic FSHR variants causing resistant ovarian syndrome. This study expands the genotypic spectrum of pathogenic FSHR variants and our knowledge of phenotype-genotype correlations.
| S-EPMC7005632 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age typically presenting with chronic oligo- or anovulation, clinical, or biochemical hyperandrogenism and polycystic ovarian morphology (PCOM). Restoring mono-ovulation is the ultimate goal of ovulation induction and most women do respond to ovulation inducing agents causing their Follicle-stimulating hormone (FSH) levels to rise. Familial clustering and the results from twin studies strongly support an underlying genetic basis for PCOS. Recent Genome wide association studies (GWAS) have identified several genetic variants being genome wide significantly associated with PCOS. Amongst those are variants in or near the Luteinizing hormone (LH) and FSH receptor genes as well as a variant in the FSH-β gene. The aim of this review is to summarize the available evidence as to whether single nucleotide polymorphisms are able to modify the PCOS phenotype or whether they constitute a risk factor for the syndrome. Data on the role of FSHR polymorphisms in PCOS are conflicting. It seems that in large Chinese studies FSHR polymorphisms are not associated with either PCOS risk or with PCOS treatment outcome. However, in large scale studies in Caucasians these polymorphisms seem to influence the risk of having PCOS. Moreover, these studies also showed that some polymorphisms might affect some clinical features of PCOS as well as treatment outcome. Although most research has focussed on the role of FSHR polymorphisms there seems to be also some evidence showing that single nucleotide polymorphisms (SNPs) in the LHCG-Receptor as well as those in FSH-β gene might also alter the phenotype of PCOS. In conclusion most studies confirm that FSHR polymorphisms do alter the phenotype of PCOS in that they either alter the response to exogenous FSH or hat they increase the risk of having PCOS.
| S-EPMC6379247 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, affecting up to 16.6% of reproductive-age women. PCOS symptoms in adolescents comprise oligomenorrhoea/amenorrhoea and biochemical and/or clinical hyperandrogenism. Long-term health risks of PCOS patients include infertility, metabolic syndrome, type 2 diabetes and cardiovascular disease. Genetic factors have been proven to play a role in development of the syndrome and its symptoms. To investigate single nucleotide variants (SNVs) in the GNRHR, ESR2, LHCGR and FSHR genes in adolescent patients with PCOS and their association with PCOS symptoms. We conducted a cross-sectional study comprising of 152 adolescents: 63 patients with PCOS, 22 patients at risk of developing PCOS and 67 healthy controls. Participants were recruited from out-patients attending a gynaecologist at the Children's Clinical University Hospital, Riga, Latvia, between January 2017 and December 2020. Genomic DNA was extracted from whole blood, and SNVs in the GNRHR, ESR2, LHCGR and FSHR genes were genotyped. The distributions of SNV genotypes were compared among the three groups and genotype-phenotype associations within the PCOS group were evaluated. No statistically significant differences were found in the distributions of genotypes for GNRHR (rs104893837), ESR2 (rs4986938), LHCGR (rs2293275) and FSHR (rs6166, rs6165, rs2349415) among PCOS patients, risk patients and healthy controls. Within the PCOS group, ESR2 rs4986938 minor allele homozygous patients had a significantly higher level of total testosterone than major allele homozygous patients and heterozygous patients. A significantly higher total testosterone level was also observed in PCOS patients carrying the LHCGR rs2293275 minor allele compared with major allele homozygous patients. The SNVs ESR2 rs4986938 and LHCGR rs2293275 play a role in the phenotypic characteristics of PCOS. To fully uncover their influence on the development of PCOS and its symptoms, further studies of larger cohorts and a follow up of this study sample through to adulthood are required. Furthermore, studies of adolescent PCOS patients conducted prior to the latest European Society of Human Reproduction and Embryology (ESHRE) criteria (2018) should be re-evaluated as the study groups might include risk patients according to these updated criteria, thereby potentially significantly impacting the published results.
| S-EPMC8700743 | biostudies-literature
Project description:BackgroundTwo polymorphisms, rs6165 and rs6166 located in the intracellular domain of FSHR has been reported to affect folliculogenesis, steroidogenesis and oocyte maturation. Several studies have highlighted the role of FSHR polymorphisms in PCOS but the findings are conflicting. A meta-analysis was carried out to decipher the emerging perspectives.MethodologyA comprehensive literature search was made using PubMed, PCOSkb, and Google Scholar. New Ottawa Scale has been utilized to evaluate the quality of each article. To evaluate the strength of association under different genetic models of rs6165 and rs6166 polymorphisms, odds ratio with a 95% confidence interval (CI) was calculated.ResultsA total of 20 articles were selected for the present study. In pooled analysis and after the stratification by ethnicity, polymorphism rs6165 remains unrelated to the onset of PCOS. Besides, rs6166 exhibits significant protection in the Indian population under recessive, additive, and allele models (OR = 0.7, CI: 0.54-0.9, p = 0.006, OR = 0.65, CI: 0.48-0.89, p = 0.006, OR = 0.82, CI: 0.7-0.95, p = 0.01, respectively) and low to moderate risk in the Caucasian population under allele model (OR = 1.17, CI: 1.04-1.32, p = 0.01).ConclusionThis meta-analysis suggests that GG genotype of rs6166 provides protection against PCOS, in a population-specific manner.
| S-EPMC10472705 | biostudies-literature
Project description:ObjectiveMultiple genetic variants have been studied for years to try to find an association with polycystic ovary syndrome (PCOS). This meta-analysis will investigate if there are associations between increased risk of PCOS and rs6165 polymorphism in follicle stimulating hormone receptor (FSHR) gene and rs2479106 polymorphism in differentially expressed in Differentially Expressed in Normal and Neoplastic Development Isoform 1A (DENND1A) gene.MethodsStudies were identified from PubMed library, and case-control studies with correct polymorphisms and available genotype frequencies were included. The statistical analysis is done in Review Manager 5.3, and odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated to see if any association with PCOS exists.ResultsIn the study of FSHR gene, eight articles with 1539 cases and 1877 controls were included. No relations were found between PCOS and rs6165 polymorphism in neither the allelic (OR=1.07, 95% CI=0.97-1.19, p=0.18), recessive (OR=1.21, 95% CI=0.98-1.50, p=0.07) nor the dominant (OR=1.05, 95% CI=0.91-1.20, p=0.53) model. The rs2479106 polymorphism in DENND1A gene included 10 studies with 3627 cases and 20325 controls. Only the Asian subgroup in the recessive model (OR=1.84, 95% CI=1.19-2.85, p=0.006) showed a positive relation with PCOS, while associations were not found within the overall results in the allelic (OR=1.09, 95% CI=0.98-1.21, p=0.10), recessive (OR=1.26, 95% CI=0.73-2.19, p=0.41) or the dominant (OR=1.31, 95% CI=1.00-1.71, p=0.05) model.ConclusionsThis meta-analysis suggests that rs2479106 polymorphism in DENND1A gene is associated with increased risk of PCOS in the Asian population. No relations were found with increased risk of PCOS and rs6165 polymorphism in FSHR gene.
| S-EPMC10065767 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a common and complex multisystemic genetic disease. Previous genome-wide association study (GWAS) of PCOS has found several potentially causative single nucleotide polymorphisms (SNPs) in Han Chinese population. The goal of present investigation was to assess the potential association between rs1121980, rs1421085, rs1558902, rs8050136 SNPs and PCOS. In order to make a better elucidation of this disease, further investigations of association between SNPs susceptibility and PCOS become necessary.In the present study, we enrolled 212 patients with PCOS and 198 control subjects. Four polymorphisms of FTO gene (rs1121980, rs1421085, rs1558902, rs8050136) were genotyped by Taqman-MGB method, and their relationship with PCOS was speculated.The allele frequency has no significant difference between the PCOS group and the controls. Genotype frequencies of the four SNPs in the additive, dominant and recessive models showed no significant difference between PCOS cases and controls.Our results demonstrate that FTO gene has little association in PCOS development.
| S-EPMC4680510 | biostudies-literature
Project description:ContextA genome-wide association study has identified three loci (five independent signals) that confer risk for polycystic ovary syndrome (PCOS) in Han Chinese women. Replication is necessary to determine whether the same variants confer risk for PCOS in women of European ancestry.ObjectiveThe objective of the study was to test whether these PCOS risk variants in Han Chinese women confer risk for PCOS in women of European ancestry.DesignThis was a case-control study.SettingThe study was conducted at deCODE Genetics in Iceland and two academic medical centers in the United States.PatientsCases were 376 Icelandic women and 565 and 203 women from Boston, MA, and Chicago, IL, respectively, all diagnosed with PCOS by the National Institutes of Health criteria. Controls were 16,947, 483, and 189 women not known to have PCOS from Iceland, Boston, and Chicago, respectively.InterventionThere were no interventions.Main outcomesMain outcomes were allele frequencies for seven variants in PCOS cases and controls.ResultsTwo strongly correlated Han Chinese PCOS risk variants on chromosome 9q33.3, rs10986105[C], and rs10818854[A], were replicated in samples of European ancestry with odds ratio of 1.68 (P = 0.00033) and odds ratio of 1.53 (P = 0.0019), respectively. Other risk variants at 2p16.3 (rs13405728), 2p21 (rs12468394, rs12478601, and rs13429458), and 9q33.3 (rs2479106), or variants correlated with them, did not associate with PCOS. The same allele of rs10986105 that increased the risk of PCOS also increased the risk of hyperandrogenism in women without PCOS from Iceland and demonstrated a stronger risk for PCOS defined by the National Institutes of Health criteria than the Rotterdam criteria.ConclusionsWe replicated one of the five Chinese PCOS association signals, represented by rs10986105 and rs10818854 on 9q33, in individuals of European ancestry. Examination of the subjects meeting at least one of the Rotterdam criteria for PCOS suggests that the variant may be involved in the hyperandrogenism and possibly the irregular menses of PCOS.
| S-EPMC3387396 | biostudies-literature