scholarly journals Genes for Enzymes Regulating Dehydroepiandrosterone Sulfonation Are Associated with Levels of Dehydroepiandrosterone Sulfate in Polycystic Ovary Syndrome

2007 ◽  
Vol 92 (7) ◽  
pp. 2659-2664 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Heath J. Antoine ◽  
Ricardo Azziz
Keyword(s):  
Los Angeles ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Dehydroepiandrosterone Sulfate ◽  
Nucleotide Polymorphisms ◽  
Adrenal Androgen ◽  
Ovary Syndrome ◽  
Dheas Level

Abstract Context: The adrenal androgen (AA) metabolite dehydroepiandrosterone sulfate (DHEAS) is often elevated in women with polycystic ovary syndrome (PCOS); AA excess in PCOS appears to be, in part, a heritable trait. Dehydroepiandrosterone (DHEA) sulfonation is controlled by the enzymes DHEA sulfotransferase (SULT2A1) and steroid sulfatase (STS). Polymorphisms in these genes have not been evaluated as modulators of DHEAS level in PCOS. Objective: The aim was to test the hypothesis that variants in the SULT2A1 and STS genes are associated with DHEAS levels in women with PCOS. Design: Women with and without PCOS were genotyped for seven single nucleotide polymorphisms (SNPs) in SULT2A1 and seven SNPs in STS. SNPs and haplotypes were determined and tested for association with DHEAS. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 white women with PCOS and 187 controls participated in the study. Main Measurements: SULT2A1 and STS genotype and DHEAS levels were measured. Results: In women with PCOS, SNP rs182420 in SULT2A1 was associated with DHEAS (P = 0.0035). Two haplotypes carrying the minor allele of rs182420 were also associated with DHEAS (P = 0.04 each). Variants within STS were not associated with DHEAS level. No associations were observed in control women. Conclusion: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.

scholarly journals Association of CYP3A7*1C and Serum Dehydroepiandrosterone Sulfate Levels in Women with Polycystic Ovary Syndrome

2008 ◽  
Vol 93 (7) ◽  
pp. 2909-2912 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Ning Xu ◽  
Ricardo Azziz
Keyword(s):  
Los Angeles ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Adrenal Androgen ◽  
Androgen Excess ◽  
Ovary Syndrome

Abstract Context: Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS. Objective: The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels. Design: Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA). Participants: A total of 287 white women with PCOS and 187 controls were studied. Main Measurements: CYP3A7*1C genotype, PCOS risk, and androgen levels were measured. Results: PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk. Conclusion: This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.

scholarly journals Variants in the 5α-Reductase Type 1 and Type 2 Genes Are Associated with Polycystic Ovary Syndrome and the Severity of Hirsutism in Affected Women

2006 ◽  
Vol 91 (10) ◽  
pp. 4085-4091 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Nissar A. Shah ◽  
Heath J. Antoine ◽  
Marita Pall ◽  
Xiuqing Guo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Los Angeles ◽  
Single Nucleotide Polymorphisms ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Single Nucleotide ◽  
Control Subjects

Abstract Context: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5α-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). Objective: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women. Design: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 White women with PCOS and 187 controls participated. Main Measurements: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed. Results: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5α-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women. Conclusions: This study presents genetic evidence suggesting an important role of both isoforms of 5α-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.

scholarly journals Association study of AMP-activated protein kinase subunit genes in polycystic ovary syndrome

2009 ◽  
Vol 161 (3) ◽  
pp. 405-409 ◽  
Author(s):  
Kari Sproul ◽  
Michelle R Jones ◽  
Ricardo Azziz ◽  
Mark O Goodarzi
Keyword(s):  
Protein Kinase ◽  
Polycystic Ovary Syndrome ◽  
Multiple Testing ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Ovary Syndrome ◽  
Component Traits ◽  
Amp Activated Protein Kinase

ObjectiveTo examine the genes for AMP-activated protein kinase (AMPK) subunits α2 (PRKAA2) and γ3 (PRKAG3) as candidates for polycystic ovary syndrome (PCOS) and its component traits.Design and methodsA total of 287 white PCOS women were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham and 187 white control subjects were recruited from the surrounding community. Seven PRKAA2 single nucleotide polymorphisms (SNPs) and four PRKAG3 SNPs were genotyped in PCOS cases and controls. Genotyping and association analysis were performed at Cedars-Sinai Medical Center.ResultsNominal associations of PRKAA2 variants with insulin-related traits and the PRKAG3 Pro71Ala variant with PCOS were not statistically significant after multiple testing correction. Among PCOS patients, there were no associations between variants in AMPK subunit genes and androgenic or reproductive traits.ConclusionsVariants in genes for AMPKα2 and AMPKγ3 were not associated with PCOS or its component traits. Our evidence does not demonstrate that AMPK is a major genetic risk factor for PCOS.

scholarly journals Variants in SULT2A1 Affect the DHEA Sulphate to DHEA Ratio in Patients With Polycystic Ovary Syndrome But Not the Hyperandrogenic Phenotype

2013 ◽  
Vol 98 (9) ◽  
pp. 3848-3855 ◽  
Author(s):  
Yvonne V. Louwers ◽  
Frank H. de Jong ◽  
Nathalie A. A. van Herwaarden ◽  
Lisette Stolk ◽  
Bart C. J. M. Fauser ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Variants ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Significant Snps ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Hormone Levels

Context: Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS. Objective: The objective of the study was to determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS. Design: This was a candidate-gene study. Patients: The discovery set consisted of 582 patients and 2017 controls. Main Outcome Measures: A pruned subset of 28 single-nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested, and we studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients. Results: None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of −0.095 (P = .027). However, carrying the minor T allele did not contribute to differences in the hyperandrogenic phenotype, including the levels of T and androstenedione, of PCOS patients. Conclusions: Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed.

Genetic polymorphisms of reproductive hormones and their receptors in assisted reproduction technology for patients with polycystic ovary syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yulia A. Koloda ◽  
Yulia V. Denisova ◽  
Natalia M. Podzolkova
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Assisted Reproductive Technologies ◽  
Polycystic Ovary ◽  
Ovarian Response ◽  
Reproductive Technologies ◽  
Reproductive Hormones ◽  
Current Data ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Art Programs

Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of childbearing, which is defined by the accumulation of multiple, small fluid-filled ovarian cysts without the selection of a single dominant follicle. Most PCOS phenotypes are characterized by the absence of spontaneous ovulation, resistance toward ovulation inductors, the production of a large immature oocytes number, and the high prevalence of ovarian hyperstimulation syndrome, resulting in reduced assisted reproductive technologies (ART) programs effectiveness. The review analyses current data about the relationship between polymorphism genotypes of KISS genes, follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and their receptors genes, gonadotropin-releasing hormone (GnRH), estrogen, and progesterone receptors genes, the PCOS risk and the features of ovarian response to stimulation during ART cycles. The use of single nucleotide polymorphisms (SNPs) as prognostic markers of ART programs outcomes would provide a personalized approach to the drugs and doses choice for ovarian stimulation and significantly increase the chance of pregnancy.

scholarly journals Alarin/FSH Ratio Might Be A New Biological Marker in Polycystic Ovary Syndrome Women with Normal and Women with Obese

2019 ◽  
Vol 3 (5) ◽  
Keyword(s):  
Luteinizing Hormone ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Biological Marker ◽  
Dehydroepiandrosterone Sulfate ◽  
Normal Weight ◽  
Control Group ◽  
Total Testosterone ◽  
Ovary Syndrome

Neuropeptides coordinate and regulate physiological processes in all animals. Alarin is a 25 amino acid neuropeptide which promotes the secretion of luteinizing hormone (LH). It has been known that serum luteinizing hormone levels are increased in women with polycystic ovary syndrome. Therefore, purpose of this was to examine the association of circulating gonadotropin secretions, and alarin with women with polycystic ovary syndrome, and to compare these findings with those of control subjects in an effort to better understand the pathophysiology of PCOS. 28 participants with a diagnosis of PCOS with normal weight and 28 participants with a diagnosis of PCOS with obese and 28 control group participants were included in this case-control study. Hormone profiles of the participants (alarin, insulin, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-SO4 ), lipid profiles total testosterone, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol) and fasting blood sugar (FBS) values were measured. Results: Serum androgens were elevated in the PCOS. Blood LH was also elevated (P < 0.05) but was higher in PCOS than Control. Patients with PCOS had an increased alarin compared with controls. LH/FSH ratio and Alarin /FSH ratio were greater than 2.1, 2.4, respectively. The blood alarin levels were significantly correlated with the serum LH levels (r=0.492, p=0.002) and the LH/FSH ratios (r=0.450, p<0.001) and Alarin/ FSH ratios. The FSH/LH and alarin /FSH ratio were elevated in the PCOS. Based on these results, the FSH/LH and Alarin /FSH ratio appears to be a useful marker of PCOS.

scholarly journals Sex Modifies the Effect of Genetic Risk Scores for Polycystic Ovary Syndrome on Metabolic Phenotypes

2021 ◽  
Author(s):  
Ky'Era V. Actkins ◽  
Genevieve Jean-Pierre ◽  
Melinda C. Aldrich ◽  
Digna R. Velez Edwards ◽  
Lea K. Davis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Risk ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Ovary Syndrome ◽  
Biological Variables ◽  
Increased Risk ◽  
The Relationship

Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). Furthermore, while only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the relationship between PCOS and its comorbidities by conducting bidirectional genetic risk score analyses in both sexes. We conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to understand the pleiotropic effects of PCOS genetic liability across 1,380 medical conditions in females and males recorded in the Vanderbilt University Medical Center electronic health record (EHR) database. After adjusting for age and genetic ancestry, we found that European descent males with higher PCOSPRS were significantly more likely to develop cardiovascular diseases than females at the same level of genetic risk, while females had a higher odds of developing T2D. Based on observed significant associations, we tested the relationship between PRS for comorbid conditions (e.g., T2D, body mass index, hypertension, etc.) and found that only PRS generated for BMI and T2D were associated with a PCOS diagnosis. We then further decomposed the T2DPRS association with PCOS by adjusting the model for measured BMI and BMIresidual (enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. This was further supported in a mediation analysis, which only revealed clinical BMI measurements, but not BMIresidual, as a strong mediator for both sexes. Overall, our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but these associations are only apparent when PCOSPRS is explicitly modeled. It is possible that these pathways are less explained by the direct genetic risk of metabolic traits than they are by the risk factors shared between them, which can be influenced by biological variables such as sex.

scholarly journals Association analysis between the polymorphisms of HSD17B5 and HSD17B6 and risk of polycystic ovary syndrome in Chinese population

2015 ◽  
Vol 172 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Rong Ju ◽  
Wei Wu ◽  
Juan Fei ◽  
Yufeng Qin ◽  
Qiuqin Tang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Chinese Population ◽  
Chinese Women ◽  
Polycystic Ovary ◽  
Control Group ◽  
Model Assessment ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Significant Difference ◽  
High Level

ObjectiveTo assess whether single nucleotide polymorphisms of HSD17B5 (AKR1C3) (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in a Chinese population.DesignA case–control study was conducted to investigate the relation between HSD17B5 and HSD17B6 polymorphisms and PCOS.MethodsIn this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected by the TaqMan method.Results and conclusionsWe found that the genotypic frequencies of the rs1937845 polymorphism were different in subjects with PCOS compared with control, with the CT genotype being more commonly found in patients with PCOS than in controls (P=0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS vs the control group (adjusted odds ratio (OR), 1.74; 95% CI=1.19–2.54; P=0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47; 95% CI=1.07–2.03; P=0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P=0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms rs12529 of HSD17B5 and rs898611 of HSD17B6 between patients with PCOS and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in patients with PCOS. In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. The CT genotype and T allele frequency are influenced significantly to a higher extent in patients with PCOS than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.

scholarly journals Polycystic ovary syndrome: clinical and laboratory evaluation

1996 ◽  
Vol 114 (4) ◽  
pp. 1222-1225 ◽  
Author(s):  
Marcos Yorghi Khoury ◽  
Edmund Chada Baracat ◽  
Dolores Perovano Pardini ◽  
Mauro Abi Haidar ◽  
Eduardo Leme Alves da Motta ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Laboratory Tests ◽  
Late Onset ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Laboratory Evaluation ◽  
Clinical Feature ◽  
Age At Menarche ◽  
Ovary Syndrome

OBJECTIVE: To evaluate clinically, and with laboratory, tests, women with polycystic ovary syndrome (PCO). PATIENTS: One hundred and twelve women with PCO were studied. METHODS: The following data was recorded: Current age; age at menarche; menstrual irregularity, occurrence of similar cases in the family; fertility, obstetric history; body mass index (BMI); and presence of hirsutism. Serum measurements of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, free testosterone, and dehydroepiandrosterone sulfate were taken. RESULTS: All patients presented either oligomenorrhea (31 percent), periods of secondary amenorrhea (9 percent), or both alterations (60 percent). The majority of the patients were infertile (75.6 percent). The LH/FSH ratio was higher than 2:1 in 55 percent of the patients and higher than 3:1 in 26.2 percent. The ultrasonographic aspect of the ovaries was considered to be normal in 31 percent. CONCLUSION: The main clinical feature of the PCO is the irregularity of menses since menarche, and that the laboratory tests would be important to exclude other disorders such as hyperprolactinemia or hyperandrogenemia caused by late-onset congenital adrenal hyperplasia.

scholarly journals Serum Melatonin in Women with Polycystic Ovary Syndrome

Folia Medica ◽  
2013 ◽  
Vol 55 (2) ◽  
pp. 10-15 ◽  
Author(s):  
Dora D. Terzieva ◽  
Maria M. Orbetzova ◽  
Mitko D. Mitkov ◽  
Nonka G. Mateva
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Immunoreactive Insulin ◽  
Total Testosterone ◽  
Melatonin Level ◽  
Night Time ◽  
Ovary Syndrome ◽  
Healthy Women

ABSTRACT There has been a surge of interest in recent years in studying the changes of serum melatonin concentrations in disorders that are associated with insulin resistance such as diabetes mellitus type 2 and polycystic ovary syndrome (PCOS). AIM: The present study was designed to investigate the day-time and night-time levels of serum melatonin and the cortisol rhythm in women with PCOS and compare them with those of healthy women. PATIENTS AND METHODS: This is a case-control study which included 30 women with PCOS and 25 healthy women. All hormonal measurements in both the study group and controls were carried out between days 3 and 5 counted from the beginning of the last regular menstrual cycle; they included serum levels of melatonin and cortisol at 03:00 a.m and 08:00 a.m, total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), follicle stimulating hormone (FSH), and immunoreactive insulin at 08:00 a.m. RESULTS: Women with PCOS were found to have a significantly higher melatonin level at 08:00 a.m. and smaller mean night-day difference in the concentrations of melatonin in comparison with those of healthy women (natural log (Ln) night-day difference 0.60 ± 0.10 pg/ml versus 1.15 ± 0.14, p < 0.002). Melatonin to cortisol ratios at 03:00 a.m. and 08:00 a.m. showed no statistically significant differences between the two groups (Ln melatonin/ cortisol 03:00 a.m., 1.01 ± 0.06 versus 1.05 ± 0.05; Ln melatonin/cortisol at 08:00 a.m., 0.62 ± 0.01 versus 0.56 ± 0.03, p > 0.05). CONCLUSION: The results we obtained about the changes of melatonin in women with PCOS could help in elucidating the complex pathophysiological pattern of this disease.

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