Preliminary study showing no association between G238A (rs361525) tumor necrosis factor-α (TNF-α) gene polymorphism and its serum level, hormonal and biochemical aspects of polycystic ovary syndrome

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.

Association of Prx4, Total Oxidant Status, and Inflammatory Factors with Insulin Resistance in Polycystic Ovary Syndrome

“…Our findings showed that TNF- α level was significantly associated with Prx4. The presence of chronic inflammation may activate this defense process by affecting the antioxidant system [ 13 ]. Chronic inflammatory markers enhance insulin resistance and hyperandrogenism; therefore, those are involved in the pathogenesis of PCOS [ 40 ].…”

“…TNF- α is a proinflammatory cytokine, which is secreted by granulose-luteal cells, ovarian macrophages, and immune cells [ 11 ]; it interferes in inflammation and immune responses [ 12 ]. TNF- α has a role in PCOS patients with obesity and hyperandrogenism [ 13 ].…”

A network pharmacological approach to evaluate Jia-Wei-Xiao-Yao-san formula’s mechanistic pathways and its implication in the symptomatology of polycystic ovarian syndrome

“…82 As the interaction between TNF and INS exists in Figure 4C, there may be an implication of TNF polymorphism associated with PCOS development, but the high serum levels of TNF-alpha were definitively increased in PCOS patients. 83,84 TNFalpha is especially high in obesity-PCOS compared with normalweight female subjects. 85 The different mechanisms modulated by TNF-alpha and IL-6 negatively affect insulin signaling, via decreased adiponectin signaling and glucose transporter type 4 protein, which effect is exacerbated in the endometrium of obese PCOS women leading to an abnormal endometrial response to androgen and insulin stimulation and consequently leading to a reproductive failure.…”

Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women

“…A study among Iranian women reported that there may be an association between PCOS susceptibility and IL17A rs2275913 and IL32 rs9927163 SNPs 101 . However, another Iranian study found no significant association between PCOS and the rs361525 polymorphism of the TNF gene 102 . According to a meta‐analysis of PCOS studies, the risk of this disorder is not associated with the –1031 T/C, –308G/A, or –805C/T polymorphism of TNF 103 .…”

“…101 However, another Iranian study found no significant association between PCOS and the rs361525 polymorphism of the TNF gene. 102 According to a meta-analysis of PCOS studies, the risk of this disorder is not associated with the -1031 T/C, -308G/A, or -805C/T polymorphism of TNF. 103 Another study similarly reported that there is probably no association between PCOS susceptibility and the -308G/A sequence variation of TNF.…”