Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome

Schweighofer, Natascha; Lerchbaum, Elisabeth; Trummer, Olivia; Schwetz, Verena; Pilz, Stefan; Pieber, Thomas R.; Obermayer–Pietsch, Barbara

doi:10.1016/j.gene.2012.04.050

Cited by 17 publications

(14 citation statements)

References 56 publications

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“…A total of 39 observational cross sectional, prospective cohort, and case control studies involving 5,121 patients and 5,059 controls were included. Of all the studies, 18 were performed in Europe [Dadachanji et al 2015;Lauritsen et al 2014;Schweighofer et al 2012;Kim et al 2012;Pangaribuan et al 2012;Schüring et al 2012;Houjeghani et al 2012;Koiou et al 2011;Tarkun et al 2004;Liu et al 2008;Li et al 2006;Sieminska et al 2004;Richard 2002;Lin et al 2015;Jayagopal 2003;Elci et al 2016;Kim et al 2013;Danilowicz et al 2014], 18 in Asia [Zhu et al 2016;Jamil et al 2015;Baldani et al 2015;O'Reilly et al 2014;Martínez-García et al 2012;Alili and Idrizi 2014;El-Shal et al 2013;Skrgatic et al 2012;Dikmen 2011;Chae et al 2010;Oh et al 2009;Xita et al 2008;Bendlov et al 2007;Atamer et al 2008;Ferk et al 2007, Tarkun et al 2010Anttila et al 1996;Prelević 1993], 2 in Africa [Song et al 2014;Yasmin et al 2013], and 1 in North America [Kim et al 2014]. Studies used a variety of methods to identify patients with PCOS.…”

Section: Characteristics and Quality Assessment Of The Studies For Sementioning

confidence: 99%

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis

Deswal

Yadav

Dang

2017

Systems Biology in Reproductive Medicine

119

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Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta-analysis was performed to examine the associations of SHBG with PCOS and to correlate serum SHBG levels with various PCOS associated endocrine and metabolic dysregulation as well as to determine the effects of various therapeutic agents on serum SHBG levels in PCOS patients in order to assess the true accuracy of SHBG in the prediction of PCOS. A literature search was performed using Pub-Med, Science direct, google scholar, EMBASE, and Cochrane library. A total of 675 relevant records were identified, of which 62 articles were included. Meta-analysis using a random-effects model was performed using STATA version 13 to calculate standardized mean difference (SMD) with 95% confidence intervals (95 % CIs). SHBG levels in controls were significantly higher than that of PCOS patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity across studies (I= 93.9% and p=0.000). Our results suggest that the lower serum SHBG levels are associated with the risk of PCOS. SHBG may also play an important role in various metabolic disturbances in PCOS patients. Therapeutic interventions improved SHBG levels in PCOS women which further reduced PCOS associated complications. Therefore, SHBG levels may prove to be a useful biomarker for the diagnosis and treatment of PCOS. Systematic review registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin.

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Section: Characteristics and Quality Assessment Of The Studies For Sementioning

confidence: 99%

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis

Deswal

Yadav

Dang

2017

Systems Biology in Reproductive Medicine

119

View full text Add to dashboard Cite

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“…While F13a has been a long-established cause of the blood clotting disorder Factor XIII Deficiency, it has recently been associated with obesity (44) and the metabolic/fertility disorder polycystic ovarian syndrome (PCOS) (45). F13a is a tetrameric zymogen that is converted by thrombin into transglutaminase (43), a calcium-regulated protein that might play a role in glucose-stimulated insulin secretion (46).…”

Section: F13a1: a Stress-inhibited Coagulation Factormentioning

confidence: 99%

An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes

et al. 2015

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Genome-wide association studies in human type 2 diabetes (T2D) have renewed interest in the pancreatic islet as a contributor to T2D risk. Chronic low-grade inflammation resulting from obesity is a risk factor for T2D and a possible trigger of β-cell failure. In this study, microarray data were collected from mouse islets after overnight treatment with cytokines at concentrations consistent with the chronic low-grade inflammation in T2D. Genes with a cytokine-induced change of >2-fold were then examined for associations between single nucleotide polymorphisms and the acute insulin response to glucose (AIRg) using data from the Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium. Significant evidence of association was found between AIRg and single nucleotide polymorphisms in Arap3 (5q31.3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12). To assess the potential relevance to islet function, mouse islets were exposed to conditions modeling low-grade inflammation, mitochondrial stress, endoplasmic reticulum (ER) stress, glucotoxicity, and lipotoxicity. RT-PCR revealed that one or more forms of stress significantly altered expression levels of all genes except Arap3. Thapsigargin-induced ER stress up-regulated both Pamr1 and Klhl6. Three genes confirmed microarray predictions of significant cytokine sensitivity: F13a1 was down-regulated 3.3-fold by cytokines, Ripk2 was up-regulated 1.5- to 3-fold by all stressors, and Steap4 was profoundly cytokine sensitive (167-fold up-regulation). Three genes were thus closely associated with low-grade inflammation in murine islets and also with a marker for islet function (AIRg) in a diabetes-prone human population. This islet-targeted genome-wide association scan identified several previously unrecognized candidate genes related to islet dysfunction during the development of T2D.

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“…Besides obesity and insulin resistance, an inflammatory atherothrombotic state with elevated proinflammatory substances (such as C-reactive protein, fibrinogen, white blood cells, plasminogen activator inhibitor-1, and endothelin-1) has also been suggested in MS, which impair endothelial function, reduce vasoreactivity and promote subclinical atherosclerosis (23). Interestingly, it has also been demonstrated that genetic variants involved in atherothrombotic diseases and blood coagulation, such as the F13A1 gene, are associated with the metabolic phenotype in PCOS (37). Thus, a common genetic background of PCOS and the MS might be related to obesity as well as to other factors such as an atherothrombotic state.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Influence of a positive family history of both type 2 diabetes and PCOS on metabolic and endocrine parameters in a large cohort of PCOS women

Lerchbaum

Schwetz

Obermayer-Pietsch

2014

European Journal of Endocrinology

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Objective: There is evidence suggesting a strong genetic background of polycystic ovary syndrome (PCOS). We aim to study the metabolic and endocrine characteristics of PCOS women with and without a family history (FHx) of type 2 diabetes mellitus (T2DM) and PCOS. Design: Cross-sectional study. Methods: We analysed the association of T2DM FHx and PCOS FHx with metabolic and endocrine parameters in 714 PCOS women. Results: A positive FHx of T2DM and PCOS were prevalent in 36.8 and 21.4% of PCOS women respectively. We found an independent association of T2DM FHx with central fat accumulation, obesity, prediabetes, metabolic syndrome (MS), insulin resistance, low HDL and elevated blood pressure (P!0.05 for all). PCOS FHx was independently associated with prediabetes (P!0.05). We observed an independent association of PCOS FHx with clinical and biochemical hyperandrogenism (P!0.05 for all), whereas there was no independent association of T2DM FHx with hyperandrogenism. PCOS women with a positive FHx of both T2DM and PCOS had an adverse metabolic and endocrine profile including a linear increase in risk of obesity, central fat accumulation, MS, prediabetes and low HDL (P!0.05 for all). Conclusions: Our findings suggest that the assessment of FHx might allow risk stratification of PCOS women, which is important considering the high prevalence of PCOS.

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Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome

Cited by 17 publications

References 56 publications

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis

An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes

Influence of a positive family history of both type 2 diabetes and PCOS on metabolic and endocrine parameters in a large cohort of PCOS women

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