Aromatase Gene (CYP 19) Polymorphisms and Endogenous Androgen Concentrations in a Multiracial/Multiethnic, Multisite Study of Women at Midlife

Sowers, Mary Fran; Wilson, Angela; Kardia, Sharon R.; Chu, Jian; Ferrell, Robert E.

doi:10.1016/j.amjmed.2006.07.003

Cited by 50 publications

(40 citation statements)

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“…While Petry et al [13] found an association of SNP50 with hyperandrogenism in a group of girls with precocious pubarche and in a population of women with high prevalence of PCOS symptoms, our results are in accordance with those described by Jin et al [14], who did not observe differences in testosterone levels among the three genotypes of SNP50 in PCOS patients. Also, in a population of pre- and perimenopausal women, no statistical difference was found in testosterone levels considering the presence of allele A for this genetic variant [34]. Taken together, these data and the fact that similar genotypic frequencies were observed between the classic and ovulatory phenotypes of PCOS in the present study, we suggest that genetic variation at the CYP19 gene appears to not be specifically associated with PCOS heterogeneity.…”

Section: Discussionsupporting

confidence: 45%

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

Maier

Spritzer²

2012

Gynecol Obstet Invest

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Aims: To assess whether a single nucleotide polymorphism (SNP50) of the aromatase gene (CYP19) is associated with polycystic ovary syndrome (PCOS) phenotypes and to investigate the influence of this polymorphism on the response of PCOS to treatment with oral contraceptive pills (OCP). Methods: 162 hirsute women were stratified into a classic PCOS group (hyperandrogenism, ovulatory dysfunction, c-PCOS) and an ovulatory PCOS group (hyperandrogenism, ovulatory cycles, polycystic ovaries, ov-PCOS). 51 women completed a 6-month OCP trial (20 µg ethinyl estradiol + 75 µg gestodene, 21/28 days per cycle, plus 100 mg spironolactone in 32 women with moderate to severe hirsutism). We considered the presence of the polymorphic allele A (AG+AA) in comparison to the absence of the polymorphism (GG) to express results and to perform the comparisons regarding clinical variables. Results: Mean age was 23.3 ± 6.9 years. Hirsutism score was similar in c-PCOS and ov-PCOS (15 (11–20) vs. 13 (11–20)). The differences in hormone and metabolic variables between phenotypes were independent of the presence of allele A. In the OCP trial subsample, no differences were observed between genotypes after 6 months’ treatment. Conclusion: The differences between c-PCOS and ov-PCOS cannot be explained by the genetic variation at SNP50 in the CYP19 gene.

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Section: Discussionsupporting

confidence: 45%

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

Maier

Spritzer²

2012

Gynecol Obstet Invest

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“…Le niveau d'expression thymique de AIRE serait donc la résultante des effets de la balance hormonale dans laquelle les cellules se trouvent. La variabilité des niveaux d'expression basale de AIRE observée chez l'homme comme chez la femme, pourrait être le reflet des variabilités des balances hormonales (oestrogènes versus testostérone) de chaque individu et du polymorphisme d'enzymes de conversion comme l'aromatase [28].…”

Section: Conséquences En Pathologie Humaineunclassified

Prédisposition aux pathologies auto-immmunes

2017

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> Les maladies auto-immunes sont un groupe d'environ 80 pathologies différentes affectant 5 à 8 % de la population. Elles sont dues à un dysfonctionnement du système immunitaire au niveau de la tolérance thymique. Le thymus est le site d'éducation des lymphocytes T. Cet apprentissage repose sur des interactions entre les lymphocytes T et les cellules épithéliales thymiques (CET) qui expriment les protéines spécifiques de tissus périphériques. Ce mécanisme complexe est appelé tolérance centrale. Les maladies autoimmunes présentent, pour la majorité d'entre elles, une forte prévalence féminine. La comparaison des transcriptomes thymiques de femmes et d'hommes met en évidence des différences d'expression des protéines spécifiques de tissus périphériques. Dans le thymus, l'expression de ces protéines est contrôlée par le modulateur de transcription AIRE (autoimmune regulator). Une analyse translationnelle de la relation entre le sexe, les hormones et AIRE, dans des modèles cellulaires humains et murins, montre qu'après la puberté, ce facteur est moins exprimé chez la femme que chez l'homme. Les estrogènes induisent une augmentation du nombre de sites de méthylation au niveau du promoteur de Aire réprimant ainsi son expression. À partir de la puberté, les femmes auraient une efficacité diminuée du processus de tolérance centrale, ce qui entraînerait un accroissement des cellules autoréactives et de leur susceptibilité aux maladies auto-immunes. Ces observations nous amènent à nous interroger sur les effets d'une exposition croissante aux perturbateurs endocriniens, molécules estrogen-like qui, en diminuant l'expression de AIRE, conduiraient à une augmentation de la fréquence des maladies auto-immunes. < Maladies auto-immunes : une forte prévalence féminineLes maladies auto-immunes touchent 5 à 8 % de la population en Europe Occidentale et aux États-Unis. Elles comprennent 70 à 80 pathologies différentes, comme la polyarthrite rhumatoïde, le lupus érythémateux disséminé, la sclérose en plaque, le diabète de type 1, le psoriasis, la maladie de Crohn et la myasthé-nie grave. Bien qu'elles présentent une grande disparité en ce qui concerne les organes ou systèmes ciblés, les auto-anticorps sériques produits et la réponse aux traitements, une caractéris-tique épidémiologique commune a été mise en évidence pour un grand nombre de ces pathologies : une forte prévalence féminine [1] (Tableau I). Cette prédominance féminine connue depuis des décennies demeure inexpliquée bien que de nombreuses hypothèses aient été émises impliquant l'environnement hormonal, le microchimérisme foetal, l'inactivation et/ou des anomalies du chromosome X. Le système immunitaire a pour fonction de protéger l'organisme contre des infections à travers des réponses innées et/ou adaptatives. Toutefois, il est clairement établi que les maladies autoimmunes se développent suite à une rupture dans les mécanismes de tolérance centrale ou périphérique du système immunitaire. Dans chacune de ces pathologies, une inflammation chronique ou périodique contribu...

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“…Increased [Sowers et al, 2006b] Increased serum E 2 :T (TT) [Sowers et al, 2006b] Depressive symptoms (TT) [Kravitz et al, 2006a] Increased serum E 2 :T (AA þ AG) [Paynter et al, 2005] Alzheimer's disease (GG þ AG) [Livonen et al, 2004] Alzheimer's disease (GG þ GT) [Livonen et al, 2004] Increased [Somner et al, 2004] Increased serum E 2 (AA) [Somner et al, 2004] ? rs1065778…”

Section: Discussionmentioning

confidence: 99%

“…For instance, an elevation in serum E 2 levels or a fall in serum T or T:E 2 levels could all be the consequence of higher enzymatic activity of CYP19. A significantly lower serum T:E 2 was reported by Sowers et al [2006b] in premenopausal or perimenopausal African American women with TT genotype for IVS2 þ 36415C > T (rs936306) variant. In the same study, author also observed markedly lower serum T levels in Japanese women with AA genotype as compared to AG genotype for IVS2 À 23584G > A (rs749292) polymorphism.…”

Section: Cyp19a1 (Cytochrome P450 Family 19 Subfamily a Polypeptidmentioning

confidence: 95%

Genetic variability in estrogen disposition: Potential clinical implications for neuropsychiatric disorders

Grover

Talwar

Baghel

et al. 2010

American J of Med Genetics Pt B

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Variability in the physiological levels of neuroactive estrogens is widely believed to play a role in predisposition to several disorders of the central nervous system. Local biosynthesis of estrogens in the brain as well as their circulating serum levels are known to contribute to this pool of neuroactive steroids. It has been well accepted that estrogens modulate neuronal functions by affecting genesis, differentiation, excitability, and degeneration of nerve cells. These actions of estrogens appear to be more prominent in females with higher concentrations and marked variability of circulating serum levels occurring over a woman's lifetime. However, our knowledge regarding the variability of neuroactive steroid levels is very limited. Furthermore, several studies have recently reported differences in the synchronization of circulating and neuronal levels of estradiol. In the absence of reliable circulating steroid levels, knowledge of genetic variability in estrogen disposition may play a determining factor in predicting altered susceptibility or severity of neuropsychiatric disorders in women. Over the past decade, several genetic variants have been linked to both differential serum estrogen levels and predisposition to diverse types of neuropsychiatric disorders in women. Polymorphisms in genes encoding estrogen-metabolizing enzymes as well as estrogen receptors may account for this phenotypic variability. In this review, we attempt to show the contribution of genetics in determining estrogenicity in females with a particular emphasis on the central nervous system. This knowledge will further provide a driving force for unearthing the novel field of "Estrogen Pharmacogenomics." © 2010 Wiley-Liss, Inc.

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Aromatase Gene (CYP 19) Polymorphisms and Endogenous Androgen Concentrations in a Multiracial/Multiethnic, Multisite Study of Women at Midlife

Cited by 50 publications

References 19 publications

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

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

Prédisposition aux pathologies auto-immmunes

Genetic variability in estrogen disposition: Potential clinical implications for neuropsychiatric disorders

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