Tohoku J. Exp. Med., 2017 October, 243(2)

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

SHAN LI,¹ LEI ZHAO² and XIAO-HUI WAN³

¹Department of Obstetrics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
²Department of Gynecology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
³Department of Reproductive Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China

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.

keywords —— HOMA-IR; polycystic ovary syndrome; SNP; testosterone; TNF-α

© 2017 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2017, 243, 95-100

Correspondence: Xiao-Hui Wan, Department of Reproductive Medicine, First Affiliated Hospital of Xinjiang Medical University, No.137, LiYuShan South Road, Urumqi 830011, China.

e-mail: xhwan2001@yeah.net