Abstract
BackgroundPolycystic ovary syndrome (PCOS) is the main cause of female infertility. Interactions among genetic, biochemical, and immunological factors can affect the pathogenesis of PCOS. As a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) plays an important role in this regard. The present study aimed to evaluate the association of the rs361525 gene single-nucleotide polymorphism (SNP) and TNF-α serum levels with the hormonal and biochemical characteristics of PCOS in Iranian individuals.MethodsThe SNP rs361525 in the TNF-α gene was analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) in a total of 111 PCOS patients and 105 healthy females. Serum levels of TNF-α, lipid and hormone profiles, and biochemical factors were measured using enzyme-linked immunosorbent assay (ELISA) and calorimetric methods, as appropriate.ResultsThe TNF-α serum level was higher in women with PCOS compared with the control group (p < 0.0001), and it was significantly correlated with the homeostasis model assessment (HOMA) factor (r = 0.138, p < 0.05). No significant differences were found in the genotype and allelic frequencies between the two groups (p > 0.05). Higher levels and significant differences were found for the HOMA factor, luteinizing hormone/follicle-stimulating hormone (LH/FSH), testosterone, and body mass index (BMI) in the PCOS group compared with the control group (p < 0.0001). High LH/FSH ratios (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.20–3.28, p < 0.01), and high HOMA factor (OR = 5.04, 95% CI = 2.82–9.01, p < 0.001) were significantly associated with an increased risk of PCOS.ConclusionsDespite the lack of significant difference between rs361525 polymorphism of the TNF-α gene and PCOS, the serum level of TNF-α was increased in PCOS patients and positively correlated with the HOMA factor. Elevation of the LH/FSH ratio and HOMA for insulin resistance (HOMA-IR) increased the risk of PCOS. Therefore, TNF-α could indirectly contribute to PCOS progression.
Highlights
Polycystic ovary syndrome (PCOS) is the main cause of female infertility
The body mass index (BMI), waist–hip ratio (WHR), total cholesterol, and triglycerides in the PCOS group were significantly higher than they were in the healthy controls (p < 0.05), the baseline low-density lipoprotein (LDL) serum level did not reach statistical significance among the two groups (p = 0.069)
Significant differences were found in the homeostasis model assessment (HOMA) index between the healthy control and PCOS groups (p < 0.0001), and this factor was significantly higher in the obese group
Summary
Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Interactions among genetic, biochemical, and immunological factors can affect the pathogenesis of PCOS. Polycystic ovary syndrome (PCOS) is a major cause of female infertility, affecting 6–10% of women during reproductive age; it is one of the most prevalent endocrine disorders [1]. This syndrome is associated with increased risks of obesity, type 2 diabetes mellitus, hyperinsulinemia, insulin resistance, cardiovascular disease, and dyslipidemia [1, 2]. The production of TNF-α in granulosa cells in PCOS patients decreases aromatase gene expression This process occurs via the inhibition of adenylyl cyclase and the cyclic adenosine monophosphate (cAMP) signaling pathway, resulting in the reduction of 17-β-estradiol production from the ovary; elevated ovarian androgen is one of the most common characteristic of PCOS patients [11, 12]
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