Further Investigation in Europeans of Susceptibility Variants for Polycystic Ovary Syndrome Discovered in Genome-Wide Association Studies of Chinese Individuals

Brower, M.; Jones, Michelle R.; Rotter, Jerome I.; Krauss, Ronald M.; Legro, Richard S.; Azziz, Ricardo; Goodarzi, Mark O.

doi:10.1210/jc.2014-2689

Cited by 58 publications

(42 citation statements)

References 23 publications

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“…In any case, the role of severe insulin resistance and very high circulating insulin in determining the PCOS phenotype in patients with SSIR states is confirmed on both clinical and basic research studies (69). One aspect of the association between PCOS and SSIR is that, in the last two decades, it has become increasingly clear that the responsible genetic factors of PCOS linked to SSIR are quite specific, and completely different with respect to the susceptible genes of the common PCOS, as proposed by recent genome-wide association and linkage studies (22,23). In fact, a combination of linkage analysis and candidate gene screening has led to the identification of a list of genes associated with congenital lipodystrophy, either generalized or partial, that encodes protein essential for normal fat tissue development and/or function in Recently, two new inherited forms of lipodystrophies due to mutation in polymerase delta 1 (POLD1) or hormonesensitive lipase (LIPE) gene have been described (70,71).…”

Section: Severe Insulin-resistant Syndrome and Pcosmentioning

confidence: 86%

“…It has been reported that the PCOS phenotype can be found from early infancy to puberty (21). Available studies do not support the concept that the common PCOS is due to a single-gene defect, although large association studies have suggested that a cluster of genes may increase the individual susceptibility to develop it (22,23). Animal studies have also suggested that fetal exposure to androgen excess may contribute to development of the PCOS phenotype later in time (24,25).…”

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Pasquali

Diamanti-Kandarakis

Gambineri

2016

European Journal of Endocrinology

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PCOS is a clinical heterogeneous entity of female androgen excess diagnosed by exclusion of other disorders responsible for androgen excess. The concept of secondary PCOS implies that there is a primary well-defined cause leading to the PCOS phenotype with underlying androgen overproduction, regardless of the origin. In these cases, we presume the term of 'secondary PCOS' could be used. In all these conditions, the potential complete recovery of the hyperandrogenemic state as well as the remission of the PCOS phenotype should follow the removal of the cause. If accepted, these concepts could help clinicians to perform in-depth investigations of the potential factors or disorders responsible for the development of these specific forms of secondary PCOS. Additionally, this could contribute to develop further research on factors and mechanisms involved in the development of the classic and the nonclassic PCOS phenotypes. Invited author's profileRenato Pasquali is full professor of Endocrinology & Metabolism and Director of the division of Endocrinology of the S.Orsola-Malpighi Hospital, Bologna, Italy. He also heads the School of Specialization in Endocrinology and Metabolism, University Alma Mater Studiorum of Bologna, Italy. He is a member of numerous national and international scientific societies and serves on the editorial boards of international journals. His scientific interests relate to (i) the pathophysiology and treatment of the polycystic ovary syndrome; (ii) the endocrinology of obesity (sex hormones, the hypothalamic-pituitary-adrenal axis, and the endocannabinoid system).

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Section: Severe Insulin-resistant Syndrome and Pcosmentioning

confidence: 86%

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Pasquali

Diamanti-Kandarakis

Gambineri

2016

European Journal of Endocrinology

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“…This hypothesis suggests that genetics may play an important role in the pathogenesis of PCOS and that ancestral gene variants eventually found to be associated with PCOS are similar across ethnicities. Brower et al recently confirmed the existence of common susceptibility genes in different ethnicities demonstrating that at least four of the PCOS susceptibility loci (i.e., all functionally involved in androgen synthesis, insulin action, and secretion) identified in the Chinese genome-wide association studies are also associated with PCOS in European individuals [46]. Although functional studies are needed to improve our understanding of the role these genes play in PCOS pathogenesis, however, it is known that insulin resistance is a major player in the pathogenesis of NAFLD [1,[3][4][5][47][48][49].…”

Section: Role Of Geneticsmentioning

confidence: 92%

Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

2015

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Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.

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“…A number of studies have successfully used genetic risk scores to explain increasing amounts of variance in diseases such as type 2 diabetes (102) and to predict related phenotype outcomes, such as myocardial infarction from coronary artery disease SNPs (103). This approach has been successfully applied in PCOS with the use of the loci determined with the use of GWAS in Chinese (57,104) and white cohorts (65). With increasing numbers of loci for PCOS being discovered recently, there is promise for genetic testing to be incorporated into disease prediction, diagnosis, and treatment.…”

Section: Clinical Application Of Discoverymentioning

confidence: 99%

Genetic determinants of polycystic ovary syndrome: progress and future directions

Jones

Goodarzi

2016

Fertility and Sterility

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104

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The field of the genetics of polycystic ovary syndrome (PCOS) has relatively recently moved into the era of genome-wide association studies. This has led to the discovery of 16 robust loci for PCOS. Some loci contain genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in the syndrome. The next challenge facing the field is the identification of causal variants and genes and the role they play in PCOS pathophysiology. The potential for gene discovery to improve diagnosis and treatment of PCOS is promising, though there is much to be done in the field before the current findings can be translated to the clinic.

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Further Investigation in Europeans of Susceptibility Variants for Polycystic Ovary Syndrome Discovered in Genome-Wide Association Studies of Chinese Individuals

Cited by 58 publications

References 23 publications

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

Genetic determinants of polycystic ovary syndrome: progress and future directions

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