Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women

Kidokoro, Kumiko; Ino, Kazuhiko; Hirose, Kaoru; Kajiyama, Hiroaki; Hosono, Satoyo; Suzuki, Takeshi; Kawase, Takakazu; Hiraki, Akio; Hamajima, Nobuyuki; Tanaka, Hideo; Tajima, Kazuo; Kikkawa, Fumitaka; Matsuo, Keitaro

doi:10.1038/jhg.2008.11

Cited by 21 publications

(10 citation statements)

References 34 publications

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“…64 Despite the limited number of studies evaluating estrogen levels in PE, it is possible to infer that not only are androgen levels altered in patients with PE, but also the testosterone/ estradiol ratio (T/E 2 ) is increased. [66][67][68] The T/E 2 is considered a measure of the functionality of aromatase, the enzyme that catalyzes, among other reactions, the conversion of testosterone into estradiol. Recently, more accurate methods have been used to measure steroids, such as gas chromatography/mass spectrometry (GC/MS), which allows the identification and more specific quantification of androgens, estrogens, and their metabolites and is considered one of the most sensitive steroidmeasuring techniques with a limit of detection of 10 pg/mL.…”

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confidence: 99%

Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

et al. 2013

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Preeclampsia (PE) remains a major cause of maternal/fetal morbidity-mortality worldwide. The first stage of PE is characterized by placental hypoxia due to a relative reduction in uteroplacental blood flow, resulting from restricted trophoblast invasion. However, hypoxia is also an essential element for the success of invasion. Under hypoxic conditions, 2-methoxyestradiol (2-ME) could induce the differentiation of cytotrophoblast cells into an invasive phenotype in culture. 2-Methoxyestradiol is generated by catechol-O-methyltransferase, an enzyme involved in the metabolic pathway of estrogens. During pregnancy, circulating 2-ME levels increase significantly when compared to the menstrual cycle. Interestingly, plasma levels of 2-ME are lower in women with PE than in controls, and these differences are apparent weeks or even months before the clinical manifestations of the disease. This article reviews the metabolic pathways involved in 2-ME synthesis and discusses the roles of these pathways in normal and abnormal pregnancies, with particular emphasis on PE.

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confidence: 99%

Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

et al. 2013

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“…These results indicated that a lack of aromatase leads to a disturbance in the balance of sex hormones and also indicates that a single base change in exon 9 of CYP19 may be directly responsible for these changes. Based on several studies that have comprehensively evaluated associations between SNPs in the CYP19 gene and levels of sex hormones (Haiman et al 2007;Cai et al, 2008;Kidokoro et al 2009), we believe that significant CYP19 gene polymorphisms may alter hormone levels to varying degrees. In particular, imbalance of the estrogen/androgen ratio, rather than individual levels of estragon or androgen, has been associated with the development of CHD (Dai et al, 2012), and Seruga et al (2014) reported that the use of aromatase inhibitors might be associated with an increased risk for CHD.…”

Section: Discussionmentioning

confidence: 99%

Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease

Wang

et al. 2016

Genetic Testing and Molecular Biomarkers

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Objective: An imbalance in sex hormone ratios has been identified in coronary heart disease (CHD), and as a key enzyme in the conversion of androgen to estrogen, aromatase plays an important role in the balance of sex hormone levels. However, there is a paucity of research into the potential roles of aromatase in CHD. In this study, we investigated associations between single-nucleotide polymorphisms (SNPs) in the CYP19 gene, which encodes aromatase, and CHD. Methods: We collected 1706 blood samples from CHD patients and control participants and used propensity score matching techniques to match case and control groups with respect to confounding factors. In a final study population, including 596 individuals, we conducted a case-control study to identify associations between three SNPs in CYP19 and CHD using v 2 or Fisher exact tests, and binary logistic regression analysis. Differences in lipid levels and parameters of echocardiography among individuals with different genotypes were assessed by one-way analysis of variance. Results: The distributions of rs2289105 alleles in the CYP19 gene differed significantly between the CHD and control groups ( p = 0.014), and the heterozygote CT genotype was associated with a significantly lower risk of CHD compared to the homozygous wild-type CC genotype ( p = 0.0063 and odds ratio = 0.575). However, blood lipid levels and echocardiographic parameters among individuals with different genotypes did not differ between the CHD and control groups. Conclusions: The CT genotype of the rs2289105 polymorphism in the CYP19 gene is associated with a decreased risk of CHD and may be a genetic marker of protection from CHD.

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“…Huhtaniemi et al [104] did not find any associations between CYP19A1 polymorphism and non-hormonal variables including anthropometric parameters, blood pressure, cognition sexual hemoglobin, blood lipids, and hemoglobin. Kidokoro et al [137] showed that SNPs in CYP19A gene alter the levels of estrogens. Eriksson et al [105] presented data showing that rs2470152 is clearly associated with serum E2 and E1 levels in men.…”

Section: Effect Of Snps On Hormonal Parametersmentioning

confidence: 99%

Genetic Polymorphisms in Aromatase (CYP19) Gene and Cancer

Warsy¹,

Al-Mukaynizi²,

Al-Daihan³

et al. 2017

Genetic Polymorphisms

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Estrogens play an important role in the development and progression of several types of cancers. The synthesis of estrogens occurs in almost all tissues of the body in addition to the gonads. The enzyme aromatase (CYP19A1) encoded by CYP19A1 gene is involved in the synthesis of estrogens. Genetic variations in CYP19A1 gene influence both the structure-function relationship of the enzyme and the rate of its synthesis. Extensive studies have reported different types of polymorphisms in the CYP19A1 gene and have shown that the polymorphisms, depending on their location in the gene, have different effects on the function and activity of the gene product. Association studies have been conducted and have led to the realization that interpopulation differences are widespread. Not only do polymorphic forms exert different effects on the development of different cancers, due possibly to the influence of other genetic variations, environmental, metabolic, and epigenetic factors, but also are important as they lead to the interindividual differences seen during treatment of the cancer state. This chapter covers important aspects of the aromatase function, the CYP19A1 gene structure, polymorphisms identified in the gene, different cancers and associated polymorphisms, and the role of the polymorphic forms in affecting the treatment strategies.

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Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women

Cited by 21 publications

References 34 publications

Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease

Genetic Polymorphisms in Aromatase (CYP19) Gene and Cancer

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