REVIEW Polymorphisms of Cytokine Genes and Polycystic Ovary Syndrome: A Review Josiane Bazzo de Alencar, MSc, 1 Hugo Vicentin Alves, MSc, 1 Laise Nayana Sala Elpidio, MSc, 1 Jeane Eliete Laguila Visentainer, PhD, 1,2 and Ana Maria Sell, PhD 1 Abstract Background: Polycystic ovary syndrome (PCOS) is the endocrinopathy that affects women in their reproductive age. The physiopathology involves multifactorial mechanisms, including cytokine gene regulation. Methods: The review was conducted in the database PubMed, with articles published between 2005 and 2015. The selected studies evaluated the single-nucleotide polymorphisms (SNPs) of cytokines genes in association with PCOS. Twenty-four studies met the inclusion criteria and showed the SNPs of cytokines that were associated or not with PCOS. Results: The disease susceptibility was associated with interleukin (IL) 1A, IL1B, IL1RN, and IL6 alleles and genotypes. The tumor necrosis factor (TNF) -1032 C/T genotype and C allele were risk factors and T/T genotype was a protector marker to disease. The IL18 SNPs were not associated with PCOS per se, but IL18- 137 C and G alleles were related to the protection of insulin resistance and glucose tolerance, respectively. One research found association between TGFB1 and PCOS. However, the TNF -308, IL10, and interferon (IFN) SNPs did not appear to influence PCOS genetic susceptibility. Conclusions: This study sought to contribute and clarify the SNPs in cytokine genes that influence the de- velopment of PCOS. Most studies occurred in Asia; most SNPs studied were in IL1B -511, TNF -1031, and IL6- 174; and most of them were associated with the susceptibility to PCOS development. Nevertheless, further investigations based on genome-wide association studies and cytokine gene SNPs are needed to better char- acterize the risk factors to PCOS. Keywords: polycystic ovary syndrome, cytokines, genetic polymorphisms, SNP Introduction P olycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy that affects women in their reproductive age. The prevalence of PCOS can reach 15%–20%, de- pending on the diagnostic criteria established to characterize the disease. 1 PCOS is characterized by anovulation, hyper- androgenism, polycystic ovary, and infertility. 2 Thus, women with PCOS may have hirsutism, obesity, insulin resistance, dyslipidemia, type 2 diabetes mellitus, and atherosclerosis. 3–5 It is also known that women with PCOS have chronic low-level inflammation, 6 and several mechanisms contribute to this and to the etiology of disease, such as aberrant lutei- nizing hormone (LH) secretion and hyperinsulinemia, in ad- dition to the environmental factors, but this is not yet entirely clear. Furthermore, the genetic factors and the immune sys- tem have an important role, once mutations and single- nucleotide polymorphisms (SNPs) in several genes are being associated with the risk of PCOS. 3,7,8 Cytokines produced by immune cells, such as IL-1, IL-6, IFN-g, and others, have been shown to affect events of reproduction such as the ovarian function. 9–13 Thus, the aim of this study was to organize a review to show the importance of several cytokine gene polymor- phisms that associate with PCOS and could be markers in the pathogenesis of disease. 1 Program of Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, State University of Maringa ´, Maringa ´, UEM, Parana ´, Brazil. 2 Immunogenetics Laboratory, Department of Basic Health Sciences, State University of Maringa ´, UEM, Maringa ´, Parana ´, Brazil. METABOLIC SYNDROME AND RELATED DISORDERS Volume XX, Number XX, 2016 Ó Mary Ann Liebert, Inc. Pp. 1–7 DOI: 10.1089/met.2016.0101 1