Dataset Information

Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic 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.

SUBMITTER: Goodarzi MO

PROVIDER: S-EPMC2453058 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.

Goodarzi Mark O MO Xu Ning N Azziz Ricardo R

The Journal of clinical endocrinology and metabolism 20080429 7

<h4>Context</h4>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.<h4>Objective</h4>The objective was to replicate the association between CYP ...[more]

PMID: 18445661

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Project description:ContextA subset of polycystic ovary syndrome (PCOS) individuals also have type 2 diabetes (T2D); an unmet need to identify this subgroup exists.ObjectiveWe looked at the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS.MethodsA total of 93 PCOS and 33 healthy controls were classified, based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A1c (HbA1c) (%) into normoglycemic (n = 34), dysglycemic (n = 33), and T2D (n = 26). Serum chemerin were measured by enzyme-linked immunosorbent assay. Homeostatic model 2 assessment of insulin resistance (HOMA-2IR) and homeostatic model 2 assessment of β-cell function (HOMA-2β) were computed using serum C-peptide.ResultsMetabolic syndrome was present in 9.7% (National Cholesterol Education Program) of PCOS. Waist circumference, body fat (%), 2hPGPG, and HbA1c levels were significantly higher in T2D group. Serum triglycerides/high-density lipoprotein cholesterol (TGs/HDL-c) ratio was increased in PCOS individuals with T2D; no significant changes in total cholesterol and LDL-c levels were seen. Serum chemerin levels were significantly higher (P < .001) in the PCOS group. Total body fat (%), 2hPGPG, HbA1c, and TG/HDL-c ratio correlated positively with chemerin levels. Serum chemerin levels correlated positively with HOMA2IR and negatively with HOMA-2β. On receiver operating characteristic curve analysis, a serum chemerin cutoff level of greater than 309.3 ng/mL differentiated PCOS individuals with dysglycemia from those without (sensitivity 85.71%, specificity 89.47%). The Cohen kappa test revealed a substantial agreement (P < .001) between chemerin cutoff and 2hPGPG levels greater than 200 mg/dL. The present study is arguably the first ever to define a serum chemerin cutoff to distinguish PCOS individuals with T2D from those without.ConclusionElevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Further, longitudinal studies with larger samples are required to confirm this association.

Project description:Background: Recent reports have highlighted the role of monosaccharide biosynthesis in the pathogenesis of polycystic ovary syndrome (PCOS), suggesting that these processes may serve as a biomarker in PCOS. Mannose is the main monosaccharide for protein glycosylation in mammals; however, the correlation between mannose and PCOS remains largely unknown. Materials and Methods: A total of 132 Chinese Han women were recruited at Shengjing Hospital of China Medical University. Mannose levels were measured in serum samples collected from 71 patients with PCOS (29 lean, 42 obese) and 61 control subjects (28 lean, 33 obese). Receiver operating characteristics (ROC) curves were prepared to compare the diagnostic performance of mannose and hormonal parameters, individually or in combination. Multivariate logistic regression analysis was used to assess whether serum mannose levels were associated with PCOS after adjusting for other co-variables. Results: We showed that serum mannose levels were significantly increased in PCOS patients compared with control subjects regardless of obese status, and hyperandrogenic PCOS patients had higher serum mannose levels than normo-androgenic PCOS and control subjects. In addition, serum mannose levels were significantly correlated with serum androgen levels. Mannose had an area under the curve (AUC) of 73% at a cutoff value of 225.79 ng/mL with a sensitivity of 66.2% and specificity of 73.8% for predicting PCOS. There were no differences between mannose, total testosterone, free testosterone, or dehydroepiandrosterone sulfate in the reliability of predicting PCOS using the method outlined by Hanley and McNeil. Combining mannose and total testosterone resulted in a higher AUC of 83.3%, and had moderate sensitivity (78.9%) and specificity (77%) for predicting PCOS. The positive and negative predictive values were 80% and 75.8%, respectively. Multivariate logistic regression revealed that higher serum mannose levels were strongly associated with an increased risk of PCOS (P = 0.016; odds ratio, 5.623; 95% confidence interval, 1.371-23.070). Conclusion: Taken together, substantially elevated serum mannose levels are significantly associated with PCOS, highlighting the importance of further research into the role of mannose in the pathogenesis of PCOS.

Project description:BACKGROUND:Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and glutamine (Gln) have showed the anti-inflammatory and antioxidant properties. So the aim of this study is to investigate the effect of glutamine supplementation on PCOS rats. METHODS:Female Sprague-Dawley rats were randomly assigned into four groups (n =?10 /group), control group, PCOS group, PCOS+?0.5?g/kg Gln group and PCOS+?1.0?g/kg Gln group. All the PCOS rats were administrated with 6?mg/100?g dehydroepiandrosterone (DHEA) for 20 consecutive days, all the PCOS+Gln groups were intraperitoneal injected glutamine twice in the next morning after the last DHEA injection. All the samples were collected 12?h after the last administration. Ovarian histological examinations were analyzed and the concentration of serum hormone, inflammatory and oxidative stress factors were measured. RESULTS:There was no obvious ovarian histological change among the PCOS group and PCOS+Gln groups. All the detected inflammation factors [C-reactive protein, interleukin (IL)-6, IL-18, tumor necrosis factor] showed significantly higher in all the PCOS groups compared to the control group (P <?0.01), and were significantly decreased with the supplementation of 0.5?g/kg glutamine (P <?0.01). Concentrations of superoxide dismutase were significantly lower in all the PCOS groups (P <?0.01) compared to the control group, and increased significantly with the supplementation of 0.5?g/kg glutamine (P <?0.01). Serum concentrations of malondialdehyde, nitric oxide synthase and nitric oxide were significantly higher in PCOS group (P <?0.01) compared with the control group, and significantly decreased to the comparative levels of control group with supplementation of 0.5?g/kg glutamine (P <?0.01). CONCLUSION:There is low-grade inflammation and oxidative stress in DHEA-induced PCOS rats. The supplementation of 0.5?g/kg glutamine could effectively ameliorate the inflammation and oxidative stress conditions of PCOS.

Project description:IntroductionPolychlorinated biphenyls (PCBs), organic lipophilic pollutants that accumulate through diet and increase with age, have been associated with polycystic ovary syndrome (PCOS) and shown to affect microRNA (miRNA) expression. This work aimed to determine if PCBs were associated with circulating miRNAs and whether there were any correlations with serum PCB/miRNA levels and hormonal changes.Methods29 non-obese PCOS and 29 healthy control women, with similar age and body mass index (BMI), had their serum miRNAs measured together with 7 indicator PCBs (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, PCB180) using high resolution gas chromatography coupled with high resolution mass spectrometry.ResultsIn the combined study cohort, four miRNAs (hsa-miR-139-5p, hsa-miR-424-5p, hsa-miR-195-5p, hsa-miR-335-5p) correlated with PCBs, but none correlated with metabolic parameters. hsa-miR-335-5p correlated with FSH. When stratified, 25 miRNAs correlated with PCBs in controls compared to only one (hsa-miR-193a-5p) in PCOS; none of these miRNAs correlated with the metabolic parameters of BMI, insulin resistance, or inflammation (C-reactive protein, CRP). However, of these 25 miRNAs in controls, hsa-miR-26a-5p, hsa-miR-193a-5p, hsa-miR-2110 and hsa-miR-195-5p positively correlated with luteinizing hormone (LH), hsa-miR-99b-5p and hsa-miR-146b-5p correlated with estradiol, hsa-miR-193a-5p correlated with progesterone, hsa-miR-195-5p correlated with follicle stimulating hormone (FSH), and hsa-miR-139-5p and hsa-miR-146b-5p negatively correlated with anti-müllerian hormone (AMH) (all p<0.05). hsa-miR-193a-5p in PCOS cases correlated with estradiol.ConclusionIn this cohort of women, with no difference in age and BMI, and with similar PCB levels, the miRNAs correlating to PCBs associated with menstrual cycle factors in healthy menstruating controls versus the anovulatory PCOS subjects. The PCB-associated miRNAs did not correlate with non-reproductive hormonal and metabolic parameters. This suggests that PCB effects on miRNAs may result in changes to the hypothalamo-ovarian axis that may thus affect fertility.

Project description:BackgroundLeptin may have important implications in polycystic ovary syndrome (PCOS)-related metabolic disorders. However, the changes in serum leptin levels in patients with PCOS and its predictive value for PCOS remain obscure. We intend to analyze the association between leptin and PCOS in this study.Materials and methodsThe study comprised 89 patients with PCOS and 139 individuals without PCOS. Each group was stratified as either normal- or hyper-fasting serum insulin (FSI), and lean or overweight/obese; and the patients were further categorized as normal- or hyper-androgenic. The validity of leptin toward the diagnosis of PCOS, or leptin combined with total testosterone, dehydroepiandrosterone sulfate (DHEAS), and free testosterone was estimated by receiver operating characteristic (ROC) curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. Associations between the clinical and metabolic variables and PCOS were analyzed via logistic regression.ResultsThe serum leptin levels of patients with PCOS were significantly higher than that of the control, and especially the PCOS in hyper-FSI, hyperandrogenimic and overweight/obese subgroups. The area under the ROC curve (AUC) of leptin was 74%, with cutoff value, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) 11.58 ng/mL, 77.5%, 62.6%, 57.0%, and 81.3%, respectively. Combined leptin and anti-Müllerian hormone (AMH) had the highest AUC (92.3%), excellent sensitivity (93.3%), moderate specificity (78.3%), PPV (73.5%) and NPV (94.8%). Serum leptin levels of the patients were correlated with the FSI, fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone levels. Elevated serum leptin was associated with a high risk of PCOS [P = 0.015; OR (95% CI) 1.128 (1.024-1.244)].ConclusionSubstantially elevated serum leptin is significantly associated with PCOS. These findings warrant further investigations into the function of leptin in the pathogenesis of PCOS.

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Dataset Information

Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.

Context

Objective

Design

Setting

Participants

Main measurements

Results

Conclusion

Publications

Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.

Similar Datasets

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