Genetic Variability in Antioxidative and Inflammatory Pathways Modifies the Risk for PCOS and Influences Metabolic Profile of the Syndrome

• Main Authors: Rok Herman, Mojca Jensterle, Andrej Janež, Katja Goričar, Vita Dolžan
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Metabolites
• Subjects: polycystic ovary syndrome; genetic variability; oxidative stress; inflammation; metabolic profile
• Online Access: https://www.mdpi.com/2218-1989/10/11/439

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder of multifactorial etiopathology likely to involve the interactions between genetics and lifestyle. Chronic inflammation and oxidative stress (OS) may participate in the pathophysiology of the syndrome. The question of the extent to which OS and inflammation are causally related to the development of the syndrome and metabolic complications remains unanswered. By our knowledge, the role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as an important trigger of inflammatory pathways and <i>NLRP3</i> and <i>CARD8</i> polymorphisms has never been addressed in PCOS yet. We conducted a case-control study conducting of total 169 Slovenian PCOS patients and 83 healthy blood donors. They were genotyped for polymorphisms in antioxidative (<i>SOD2</i> rs4880, <i>CAT</i> rs1001179, <i>PON1</i> rs854560, and rs662) and inflammatory pathways genes (<i>NLRP3</i> rs35829419, <i>CARD8</i> rs2043211, <i>TNF</i> rs1800629, <i>IL1B</i> rs1143623, and rs16944, <i>IL6</i> rs1800795) using competitive allele-specific polymerase chain reaction (PCR). Logistic regression and the Mann–Whitney test were used in the statistical analysis. <i>SOD2</i> rs4880, <i>CARD8</i> rs2043211, and <i>IL1B</i> rs16944 were associated with the risk of developing PCOS. Furthermore, the interactions between <i>CARD8</i> rs2043211 and <i>IL6</i> rs1800795 and between <i>IL1B</i> rs1143623 and <i>IL6</i> rs1800795 also significantly affected the risk for PCOS. With regard to glucose homeostasis, <i>CAT</i> rs1001179, <i>SOD2</i> rs4880, <i>PON1</i> rs854560, <i>NLRP3 </i>rs35829419, and <i>TNF</i> rs1800629 were significantly associated with response to the glycemic load. Our data indicate that the genetic variability in the antioxidative and inflammatory pathways influences the development of PCOS and glucose homeostasis in PCOS patients.