Aromatase Gene Polymorphism Does Not Influence Clinical Phenotype and Response to Oral Contraceptive Pills in Polycystic Ovary Syndrome Women

Maier, Polyana Sartori; Spritzer, Poli Mara

doi:10.1159/000339317

Cited by 8 publications

(6 citation statements)

References 71 publications

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“…Additionally, certain promoter variants were independently associated with PCOS symptom score in UK adolescents [ 92 ]. The rs2414096 polymorphism lacked association with PCOS or with alterations in hormonal and metabolic variables after undergoing a 6-month treatment regime of oral contraceptives in both anovulatory and ovulatory PCOS women [ 93 ]. Another common polymorphism, a tetranucleotide repeat polymorphism (TTTA) n in the fourth intron related to suboptimal aromatase activity [ 94 ], has been investigated.…”

Section: Genetics Of Pcosmentioning

confidence: 99%

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Dadachanji

Shaikh

Mukherjee

2018

Genetics Research International

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Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

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Section: Genetics Of Pcosmentioning

confidence: 99%

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Dadachanji

Shaikh

Mukherjee

2018

Genetics Research International

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“…Whilst the pathogenesis of PCOS remains largely unknown, accumulating data suggest that PCOS is a complex disease which involves both genetic and environmental factors [3,4,5]. PCOS may begin in utero, because female mammals (rhesus monkeys, sheep, mice or rats) exposed to androgen in utero develop masculinized phenotypes similar to PCOS in adulthood [6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Promoter Methylation of <b><i>CYP19A1</i></b> Gene in Chinese Polycystic Ovary Syndrome Patients

Yu¹,

Sun²,

Liu

et al. 2013

Gynecol Obstet Invest

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Aims: This study aimed to examine the methylation status of the CYP19A1 promoter region in Chinese polycystic ovary syndrome (PCOS) patients. Methods: A case-control study was designed that involved 10 PCOS patients and 10 controls. Ovary tissues obtained from 10 women with PCOS and 10 healthy controls were matched for body mass index and age. Methylation of CYP19A1 promoter was detected by methylation-specific PCR. CYP19A1 expression was measured by real-time PCR and Western blotting. Results: The methylation level of CYP19A1 promoter in PCOS samples was significantly higher than in controls (0.698 ± 0.192 vs. 0.210 ± 0.064, p < 0.01). A significant downregulation of CYP19A1 mRNA and protein expression levels was observed in PCOS ovary tissues. Furthermore, the scatter plot revealed that promoter methylation was inversely correlated with CYP19A1 mRNA level (Pearson's correlation -0.820, p < 0.01). Conclusion:CYP19A1 expression is frequently repressed in PCOS ovaries due to the promoter hypermethylation. CYP19A1 promoter hypermethylation may play a key role in the pathogenesis of PCOS.

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“…Other studies detailed in Table 4 , failed to detect gene-drug interactions, but they confirmed therapies efficiency in terms of body composition, endocrine, metabolic and ovulation improvements ( 95 , 96 , 101 , 102 , 108 – 110 ). Besides, ovulation predictors such as high FSH levels and low BMI range were identified ( 97 ).…”

Section: Pharmacogenomics In Pcosmentioning

confidence: 95%

“…After 6 months of OCP treatment, testosterone, glucose, and LH levels were reduced, and hirsutism improvements were seen. However a slight increase of lipids was also detected ( 101 , 102 ). OPC have potential adverse effects on IR, diabetes mellitus and coagulability ( 89 ), indeed Maier et al.…”

Section: Pharmacogenomics In Pcosmentioning

confidence: 98%

Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis

et al. 2020

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Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Epidemiological findings revealed that women with PCOS are prone to develop certain cancer types due to their shared metabolic and endocrine abnormalities. However, the mechanism that relates PCOS and oncogenesis has not been addressed. Herein, in this review article the genomic status, transcriptional and protein profiles of 264 strongly PCOS related genes (PRG) were evaluated in endometrial cancer (EC), ovarian cancer (OV) and breast cancer (BC) exploring oncogenic databases. The genomic alterations of PRG were significantly higher when compared with a set of non-diseases genes in all cancer types. PTEN had the highest number of mutations in EC, TP53, in OC, and FSHR, in BC. Based on clinical data, women older than 50 years and Black or African American females carried the highest ratio of genomic alterations among all cancer types. The most altered signaling pathways were p53 in EC and OC, while Fc epsilon RI in BC. After evaluating PRG in normal and cancer tissue, downregulation of the differentially expressed genes was a common feature. Less than 30 proteins were up and downregulated in all cancer contexts. We identified 36 highly altered genes, among them 10 were shared between the three cancer types analyzed, which are involved in the cell proliferation regulation, response to hormone and to endogenous stimulus. Despite limited PCOS pharmacogenomics studies, 10 SNPs are reported to be associated with drug response. All were missense mutations, except for rs8111699, an intronic variant characterized as a regulatory element and presumably binding site for transcription factors. In conclusion, in silico analysis revealed key genes that might participate in PCOS and oncogenesis, which could aid in early cancer diagnosis. Pharmacogenomics efforts have implicated SNPs in drug response, yet still remain to be found.

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Aromatase Gene Polymorphism Does Not Influence Clinical Phenotype and Response to Oral Contraceptive Pills in Polycystic Ovary Syndrome Women

Cited by 8 publications

References 71 publications

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Promoter Methylation of <b><i>CYP19A1</i></b> Gene in Chinese Polycystic Ovary Syndrome Patients

Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis

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