A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome

Küme, Tuncay; Çalan, Mehmet; Yılmaz, Özgür; Kocabaş, Gökçen Ünal; Yeşil, Pınar; Temür, Muzaffer; Biçer, Merve; Çalan, Özlem Gürsoy

doi:10.1007/s40618-016-0453-5

Cited by 38 publications

(38 citation statements)

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“…In addition, both rs1800629 and rs4645843 were significantly associated with BMI, which is consistent with the finding that TNF-α is linked to obesity (Li and Loos 2008;Bhagat et al 2010). The rs1800629 has been demonstrated to have a significant effect on TNF-α transcriptional activity and regulate the expression level of TNF-α (Deepika et al 2013;Kume et al 2016). Increased TNF-α levels in women with PCOS have been verified by most studies (Deepika et al 2016;Kume et al 2016).…”

Section: Discussionmentioning

confidence: 94%

“…The rs1800629 has been demonstrated to have a significant effect on TNF-α transcriptional activity and regulate the expression level of TNF-α (Deepika et al 2013;Kume et al 2016). Increased TNF-α levels in women with PCOS have been verified by most studies (Deepika et al 2016;Kume et al 2016). Increased TNF-α can promote insulin resistance and cause hyperandrogenism.…”

Section: Discussionmentioning

confidence: 97%

“…The SNP rs1799964 has been linked with altered promoter activity leading to varied plasma TNF-α levels in healthy subjects and repeatedly reported to be significantly associated with PCOS (Yun et al 2011;Deepika et al 2013Deepika et al , 2016. Unfortunately, the various association studies on rs1800629 have obtained conflicting results due to their relative small sample size (Deepika et al 2013;Kume et al 2016). Furthermore, rs4645843, giving rise to a Pro-to-Leu exchange at 84 position of TNF-α, has the greatest impact on the TNF-α protein structure stability based on the in silico analysis (Dabhi and Mistry 2014;Fang et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have reported that the incidence of PCOS is closely related to chronic low-grade inflammation in human ovary, while TNF-α has found to exist in the follicular fluid of ovary and oocytes (Deepika et al 2013;Kume et al 2016). In addition, PCOS patients have been found to have higher TNF-α levels than healthy women (Deepika et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…The single nucleotide polymorphism (SNP) located in the promoter region of the TNF-α gene may influence its transcription. In fact, the -308G/A (rs1800629) polymorphism has been reported to be associated with elevated serum TNF-α concentrations (Kume et al 2016). Various studies with small sample sizes have tested the association between PCOS and the rs1800629 polymorphism in TNF-α (Deepika et al 2013;Kume et al 2016).…”

Section: Introductionmentioning

confidence: 99%

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A Missense Variant rs4645843 in TNF-α Gene Is a Risk Factor of Polycystic Ovary Syndrome in the Uygur Population

Zhao

Wan

2017

Tohoku J. Exp. Med.

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Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome, resulting from the interaction of gene variants and environmental factors. PCOS is viewed as a proinflammatory state and is characterized by hyperandrogenism, hyperinsulinemia, and over-weight. In China, the incidence of PCOS is higher in the Uygur population than that in the Chinese Han population. The association of the tumor necrosis factor α (TNF-α ) gene with PCOS remains to be clarified. Here, we investigated the association of TNF-α polymorphisms with PCOS in the Uygur population (393 patients with PCOS and 381 healthy subjects). Two single-nucleotide polymorphisms in TNF-α were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method: rs1800629 (-308G/A polymorphism), a commonly tested variant and rs4645843 (6213C/T polymorphism) that causes a Pro-to-Leu substitution at position 84, the most damaging variant of TNF-α based on in silico analysis. We thus found that both the genotypic and allelic distributions of rs4645843 were significantly different between PCOS and control groups (p = 0.03 and 0.024, respectively), whereas those of rs1800629 were similar between the groups. Furthermore, rs4645843 was significantly associated with serum testosterone levels and the score of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), but no such association was found with rs1800629. Importantly, both rs4645843 and rs1800629 were significantly associated with higher body mass index (p < 0.05). This is the first study that shows the association of TNF-α gene with PCOS in the Uygur population. The TNF-α gene may influence the pathogenesis of PCOS through regulating testosterone level, obesity and HOMA-IR.

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