Investigating association of Cytokine genes with polycystic ovary syndrome (PCOS) risk: A systematic review

Investigating association of Cytokine genes with polycystic ovary syndrome (PCOS) risk: A systematic review
Mohamad Amin Talebpour,¹ Minoo Momenzadeh,² Valareza Alizadeh,^3,*
1. Student Research Committee, Islamic Azad University, Mashhad branch, Mashhad, Iran.
2. Student Research Committee, Islamic Azad University, Mashhad branch, Mashhad, Iran.
3. Student Research Committee, Islamic Azad University, Mashhad branch, Mashhad, Iran.
Introduction: Polycystic ovary syndrome (PCOS) is a common and complex gynecological endocrine disorder that affects approximately 6% to 10% of women of their reproductive age. The exact etiological mechanism of PCOS is still under debate; however, there is evidence that genetic factors play a vital role. Cytokine genes polymorphisms may play an important role in the etiology of PCOS.
Methods: This review was performed within articles published at PubMed, Scopus, and Web of Science from 2015 to 2020. The keywords were Cytokine genes; Inflammation; Polycystic ovary syndrome. By searching this database, 68 articles were found, 24 of them were not related to investigating, and 19 of them by reading abstract were removed. All articles chosen from English papers.
Results: As a common multifunctional cytokine, IL-6 has been proven to influence the processes of fertilization, implantation, and ovulation, which are also affected in women with PCOS. Some genetic studies have been performed to investigate the associations between IL−6 rs1800795 polymorphism and PCOS risk; however, the results were inconclusive. A single study lacks sufficient statistical power to confirm the relationship between rs1800795 and the risk of PCOS because of the small sample size. Some studies focused on the associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results remain controversial. A study showed that an increase in both low-grade chronic inflammation and insulin resistance in PCOS patients is associated with increased central fat excess rather than PCOS status. It remains to be established whether the proinflammatory state in PCOS is primarily a result of genetic variation or simply inflamed adipose tissue, because there is an increased prevalence of abdominal adiposity in PCOS across all weight classes. In fact, no differences were reported in levels of TNF-alpha, IL-6, and markers of inflammation between obese women with PCOS and obese controls. Furthermore, it has been suggested that obesity-associated genes, environmental factors, and dietary habits are also responsible for the increasing prevalence of PCOS worldwide.
Conclusion: Future multi-ethnicity studies of homogeneous populations of PCOS patients with larger sample sizes and well-matched controls are needed. future genetic studies should include larger sample sizes and investigation of SNPs within these genes to uncover the causal SNP variant associated with PCOS in different ancestries. Also, SNPs in inflammatory genes seem unrelated to PCOS, and require additional investigation, especially in the context of obesity and PCOS.
Keywords: Cytokine genes; Inflammation; Polycystic ovary syndrome.