Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis

Li, Yuxi; Fang, Lanlan; Yan, Yang; Wang, Zhen; Wu, Ze; Jia, Qiongqiong; Cheng, Jung‐Chien; Sun, Yingpu

doi:10.1016/j.rbmo.2020.10.003

Cited by 12 publications

(9 citation statements)

References 41 publications

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“…Several studies have explored the relationship between the SHBG rs6259 SNP and serum SHBG concentration and PCOS risk, but they present conflicting results ( Cousin et al, 2004 ; Bendlová et al, 2007 ; Ferk et al, 2007 ; Martinez-Garcia et al, 2012 ; Dai et al, 2015 ; Abu-Hijleh et al, 2016 ; Bhatnager et al, 2019 ; Liu et al, 2019 ). Our results showed that SHBG rs6259 was not associated with PCOS risk, which is in agreement with the results of studies by Li et al and Liao et al ( Liao and Cao, 2020 ; Li et al, 2021 ). Additionally, Liao et al also found that a null link between the SHBG rs727428 polymorphism and the risk of PCOS was also found under any genetic models ( Liao and Cao, 2020 ).…”

Section: Discussionsupporting

confidence: 93%

“…Single nucleotide polymorphisms (SNPs) might reveal functional changes caused by amino acid variation or gene expression regulation. Candidate gene investigations provide insight into different frequency distributions in healthy and diseased populations ( Douma et al, 2019 ); however, previous studies exploring the potential relationship between PCOS susceptibility and CYP17A1/CYP19A1/SHBG gene polymorphisms used statistically insufficient samples sizes and reported inconsistent findings ( Li et al, 2012 ; Liao and Cao, 2020 ; Li et al, 2021 ; Sharma et al, 2021 ). Thus, The search acronym (PICO) for our meta-analysis to elucidate the relationship between CYP17A1/CYP19A1/SHBG gene polymorphisms in both wild type and mutant type and PCOS susceptibility in general populations in a larger study cohort.…”

Section: Introductionmentioning

confidence: 99%

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The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis

et al. 2022

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Objective: To elucidate the relationship between CYP17A1/CYP19A1/SHBG gene polymorphisms and PCOS susceptibility.Methods: We searched multiple databases from inception to December 2020 and meta analysis was conducted to elucidate the relationship between gene polymorphisms and PCOS risk.Results: 26 studies were included, comprising 4860 PCOS and 4043 controls. CYP17A1 rs743572 polymorphisms were found to be negatively associated with PCOS risk under dominant model (p = 0.017, OR = 0.83, 95%CI 0.72–0.97, I2 = 74.80%, Pheterogeneity = 0.000) in the general population while neither CYP19A1 rs2414096 polymorphisms (p = 0.578, OR = 0.87, 95%CI 0.54–1.41, I2 = 95.90%, Pheterogeneity = 0.000) nor SHBG rs6529 polymorphisms (p = 0.752, OR = 0.99, 95%CI 0.94–1.05, I2 = 60.90%, Pheterogeneity = 0.012) was associated with PCOS susceptibility under dominant model in the general population.Conclusion: CYP17A1 rs7435721 polymorphisms might be protective factors against PCOS in general populations.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD4202122640.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis

et al. 2022

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“…SHBG is a plasma glycoprotein that regulates the action of steroid hormones including androgens and estradiol [ 48 ]. Previous researches have shown that low serum SHBG is related to obesity, insulin resistance, compensatory hyperinsulinemia, and is a biomarker for abnormal glucose and lipid metabolism, type 2 diabetes, and cardiovascular diseases [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation

Chen

et al. 2023

J Transl Med

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Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited. Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins. Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR. Conclusions RES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.

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“…Moreover, polymorphisms that occur in the sex hormone–binding globulin (SHBG) gene (chromosome 17p12—p13) seem to be crucial: it has been shown that a shorter (TAAAA) pentanucleotide repeat is responsible for an altered gene transcription [ 51 ]. As a consequence, poor circulating levels of SHBG cause obesity, impaired lipid metabolism, hyperinsulinemia, hyperandrogenism and chronic inflammation in women affected by PCOS [ 52 ].…”

Section: Mechanisms Involved In Pcos Pathogenesismentioning

confidence: 99%

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome

et al. 2022

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Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known about the molecular mechanisms and signaling pathways underlying the pathogenic mechanisms. In this sense, recent research has suggested that the influence of multiple factors, including age, environment, lifestyle and the disease state environment can change the clinical presentation of PCOS via epigenetic modifications. Variants in the genes encoding for proteins involved in steroidogenesis and glucose homeostasis play a crucial role in the development of the disease. Other genes involved in inflammation and cell proliferation seem to undergo an epigenetic control. Moreover, lifestyle factors influence the PCOS course and prognosis, including diet and physical activity, which are fundamental in reducing oxidative stress, inflammation and in improving metabolic and hormonal parameters. In the present review, literature evidence on molecular and epigenetic mechanisms related to PCOS etiology will be discussed, with a particular attention on the positive influence of diet and physical activity as nonpharmacological ways of intervention in the management of the disease.

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Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis

Abstract: Her research has focused on female reproductive physiology and diseases.

Cited by 12 publications

References 41 publications

The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis

The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis

Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome

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