The hallmark of pro- and anti-inflammatory cytokine ratios in women with polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrinopathy considered to be the most common metabolic disorder in women of reproductive age. Women with PCOS present with an increased risk of noncommunicable diseases (NCDs), especially low-grade chronic inflammation mediated by proinflammatory cytokines, and insulin resistance. This study aimed to investigate cytokine levels and their ratios in PCOS women compared to a healthy control group. This study evaluated 97 women with PCOS and 99 healthy women as controls. The PCOS diagnosis was performed according to ESHRE/ASRM. Plasma cytokines were evaluated by flow cytometry. We observed lower TNF levels, and decreased TNF/IL-6, TNF/IL-2, and TNF/IL-4 ratios in PCOS patients compared to the control group (p < 0.05). These results indicate an imbalance between pro- and anti-inflammatory cytokines, with prominent counter-regulatory cytokine production. These changes may be important in explaining the phenotypes present in PCOS and to direct better interventions for patients with this syndrome.

Evaluation of PCSK9 levels and its genetic polymorphisms in women with polycystic ovary syndrome.

Dyslipidemia is one of the common metabolic disorders in Polycystic Ovary Syndrome (PCOS). Proprotein convertase subtilisin kexin type 9 (PCSK9) is a new component of lipid metabolism and correlated to the development of dyslipidemia and atherosclerosis. This protein acts by preventing the recycling of LDL receptors (LDL-r) back to the cell surface and thus generates higher levels of LDLc. The objective of this study was to evaluate the PCSK9 polymorphisms rs505151 (c.2009A>G), rs562556 (c.1420A>G) and rs11206510 (T>C) and plasma PCSK9 levels in PCOS. A group of women with PCOS (n=97), and a group of healthy women (control, n=99) were selected. Biochemical parameters were determined by using Vitros system and polymorphisms were assessed by TaqMan SNP Genotyping Assays. Plasma PCSK9 levels or PCSK9 polymorphisms were not associated with PCOS. The genotype rs11206510TT was associated with higher levels of PCSK9 in both groups. The population investigated (PCOS+control groups) with the rs505151AA genotype presented higher HDLc levels. The GG genotype regarding rs562556 polymorphism was associated with higher HDLc in PCOS group, while the AA genotype carriers had higher plasma testosterone levels when evaluated all women in a same group. The results were the same by comparing recessive and dominant model despite PCOS or both groups altogether. Our results suggest that PCSK9 is not altered specifically in PCOS, but it could be associated with in lipid and androgen metabolism in Brazilian women.

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.

PURPOSE: The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. METHODS: We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. RESULTS: Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). CONCLUSIONS: Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.

Peripheral blood-derived cytokine gene polymorphisms and metabolic profile in women with polycystic ovary syndrome.

BACKGROUND: The imbalance between proinflammatory and anti-inflammatory pathways plays a role in polycystic ovary syndrome (PCOS) etiology. We aimed to investigate the relationship between polymorphisms of genes encoding inflammation-associated cytokines and the metabolic profile of Brazilian women with PCOS. DESIGN: Case-control study. METHODS: The study included 196 women - 97 with PCOS (diagnosed based on Rotterdam criteria, 2003) and 99 age-matched, healthy women (controls). It was investigated polymorphisms in cytokines genes from peripheral blood-derived DNA by using PCR. RESULTS: The frequencies of alleles, genotypes, and phenotypes were similar between women with PCOS and controls. The GG genotype of the -179C/G polymorphism (IL6) was associated with higher glucose levels, while the GA and AA genotypes of the -1082A/G polymorphism (IL10), CT and TT genotypes of the -819A/T polymorphism (IL10), CA and AA genotypes of the -522A/G (IL10) polymorphism, and TA genotype of the +874T/A polymorphism (IFN-γ) were associated with lower total cholesterol and triglycerides levels. The GA genotype of the -1082A/G polymorphism (IL10) and the CC genotype of the 10T/C polymorphism (TGF-ß1) were associated with lower and higher Ferriman indices, respectively, in women with PCOS. The AA genotype of the -1082A/G polymorphism (IL10) was associated with lower glucose levels, while the TC genotype of the 10T/C polymorphism (TGF-ß1) was associated with a lower lipid accumulation product index and higher high-density lipoprotein cholesterol levels in the PCOS group. CONCLUSIONS: The genetic polymorphisms of cytokines are not associated with PCOS development, but may contribute to common metabolic disorders associated with PCOS.

-1131T>C and SW19 polymorphisms in APOA5 gene and lipid levels in type 2 diabetic patients.

Type 2 diabetes mellitus is a metabolic, vascular, and neuropathic disease with a high risk of atherosclerotic events due to dyslipidemic states. Polymorphisms in Apolipoprotein A5 gene (APOA5) have been associated with increased triglyceride levels in many different populations. This study aimed to identify the frequencies of the APOA5 -1131T>C and SW19 polymorphisms and evaluate their effects on lipid levels in patients with type 2 diabetes. Genotyping of APOA5 -1131T>C and SW19 polymorphisms was performed by PCR-RFLP in 146 diabetic patients and in controls (n = 173), from 30 to 80 years of age. Diabetic patients were divided into two groups: patients not treated with lipid lowering drugs (group G1; n = 62) and those treated with lipid lowering drugs (group G2, n = 84). Lipids and lipoproteins were determined enzymatically. Among participants not treated with lipid-lowering drugs (diabetics G1 and controls; n = 235), the -1131C was associated with lower LDLc levels (p = 0.015). In the diabetic patients, the 19W allele was associated with higher triglyceride levels (p = 0.004). In G1 diabetic patients, the combined analysis of APOA5 -1131T>C and SW19 polymorphisms showed that [TC or CC] + SS carriers presented lower total cholesterol levels than did other genotype combinations (p = 0.049). It could therefore be concluded that APOA5 -1131T>C and SW19 polymorphisms influence lipid levels in type 2 diabetic patients.