Estrogen receptor αlpha gene (ESR1) PvuII and XbaI polymorphisms are associated to metabolic and proinflammatory factors in polycystic ovary syndrome

Silva, F.S.; Sóter, Mirelle O.; Sales, Mariana F.; Cândido, Alexandre Luna; Reis, Fernando M.; Silva, I.F.O.; Sousa, Marinez O.; Ferreira, Cláudia N.; Gomes, Karina Braga

doi:10.1016/j.gene.2015.01.037

Cited by 24 publications

(23 citation statements)

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“…Women with PCOS present a higher risk of obesity (in particular the visceral phenotype), dyslipidemia, insulin resistance (IR) with compensatory hyperinsulinemia, type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular complications (Palomba et al 2015;Silva et al 2015;Azziz et al 2016;Pavaleanu et al 2016;Carvalho et al 2017a;Papadakis et al 2017;Xavier et al 2018). Another relevant complication is infertility due to chronic anovulation (Joham et al 2015; Glintborg and Andersen 2017) ( Figure 1).…”

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confidence: 99%

“…PCOS is a condition of high prevalence (Zhao et al 2006;Tehrani et al 2011;Musmar et al 2013;Jiao et al 2014) with an important impact on the quality of life (Palomba et al 2015;Silva et al 2015;Pavaleanu et al 2016;Papadakis et al 2017). Although it is significantly expensive for the health system, the understanding of its pathophysiology is very relevant (Azziz et al 2005).…”

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confidence: 99%

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Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review

Carvalho

Reis

Cândido

et al. 2018

Endocrine Regulations

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Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.

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confidence: 99%

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confidence: 99%

Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review

Carvalho

Reis

Cândido

et al. 2018

Endocrine Regulations

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“…Dysregulation of the sympathetic nervous system is also involved in the etiology of PCOS [41]. Previous studies have demonstrated that some genetic variants of genes such as metalloproteases meprin-α (MEP1A) and estrogen receptor 1 (ESR1) are associated with glucose and insulin metabolism and inflammation in PCOS women [42,43]. In the present study, the GRS for PCOS related genes was also positive- HOMA-IR according to genetic risk factor (GRS) calculated from selected 7 SNPs from the PCOS study according to energy intake.…”

Section: Discussionmentioning

confidence: 99%

High Genetic Risk Scores of ASIC2, MACROD2, CHRM3, and C2orf83 Genetic Variants Associated with Polycystic Ovary Syndrome Impair Insulin Sensitivity and Interact with Energy Intake in Korean Women

Kim¹,

Liu²,

Jin³

et al. 2018

Gynecol Obstet Invest

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Background: We explored the genetic variants that were associated with polycystic ovary syndrome (PCOS) by genome-wide association study (GWAS) and evaluated the association of genetic risk scores (GRS) of the selected genetic variants with insulin resistance and the interaction of the GRS with nutrient intake to develop insulin resistance. Methods: The 6 genetic variants involved in brain and nervous system (acid sensing ion channel subunit 2 rs8071961, rs1988598, and rs16589, macro domain containing 2 rs7262810 CHRM3 rs1867265 and chromosome 2 open reading frame 83 rs11889798) were selected from a GWAS of the PCOS study. GRS of the 6 single nucleotide polymorphisms was calculated in 3,723 Korean women in the Ansan/Ansung cohort of KARE study. Results: Fasting serum insulin and C-reactive protein (CRP) levels, homeostasis model assessment of insulin resistance (HOMA-IR), and psychological stress levels were significantly higher in the high-GRS group than the low-GRS group. However, serum-free T4 levels were significantly lower in the high-GRS group. HOMA-IR and CRP were higher OR (1.129 and 1.382) in the high-GRS group than the low-GRS group after adjusted for covariates. There was a significant interaction between GRS and daily energy intake (p = 0.004). The OR (1.233) for HOMA-IR was higher in the high-GRS group than the low-GRS group only in the group with lower energy intakes based on estimated energy requirement. Conclusion: Women with high-GRS for PCOS had increased risk of insulin resistance and low energy intake did not protect against the elevation of insulin resistance in women with high GRS. Low energy intake might be protective against PCOS in carriers with low and medium GRS.

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“…For example, FSHR rs6166 was associated with increased PCOS risk in a study of 377 Chinese PCOS patients and 388 age-matched healthy controls (23), but not in a study in a different ethnic population (24). ESR1 rs9340799 has been associated with increased PCOS risk in a Pakistani population (25), but not in a Brazilian population (26). …”

Section: Introductionmentioning

confidence: 98%

Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study

et al. 2018

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Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with a prevalence of 6–8%. Although the etiology of PCOS has been investigated extensively, the association between genetic predisposition and PCOS risk is largely unknown. In this study, we genotyped 63 SNPs in 10 genes among 361 PCOS patients and 331 healthy controls in a Chinese Han population. The following variant alleles were significantly associated with decreased PCOS risk: ESR1 rs9340799 (P = 0.000), PPARG rs709154 (P = 0.013), and rs1151996 (P = 0.013), HMGA2 rs2272046 (P = 0.000), MTHFR rs1801133 (P = 0.000). Accordingly, the following genotypes at various loci were associated with reduced PCOS risk: GA genotype at rs9340799 (P < 0.0001) in ESR1, TA genotype at rs709154(P < 0.0001) in PPARG and CA genotype at rs2272046 (P < 0.0001) in HMGA2. Moreover, GA genotype at rs1999805 (P = 0.013) in ESR1 and TT genotype at rs1801133 in MTHFR (P < 0.0001) correlated with elevated PCOS risk. Furthermore, haplotype analysis revealed significant differences in haplotype distributions of CYP11A1, ESR2 and PPARG gene between cases and controls. In addition to confirming that ESR1 rs9340799, HMGA2 rs2272046 and MTHFR rs1801133 are related to the risk of PCOS, these findings also provide the first evidence that PPARG rs709154 and ESR1 rs1999805 are significantly associated with PCOS risk in a Chinese population. Further functional studies are warranted to elucidate the underlying biological mechanisms.

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Estrogen receptor αlpha gene (ESR1) PvuII and XbaI polymorphisms are associated to metabolic and proinflammatory factors in polycystic ovary syndrome

Cited by 24 publications

References 53 publications

Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review

Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review

High Genetic Risk Scores of <b><i>ASIC2, MACROD2, CHRM3</i></b>, and <b><i>C2orf83</i></b> Genetic Variants Associated with Polycystic Ovary Syndrome Impair Insulin Sensitivity and Interact with Energy Intake in Korean Women

Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study

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