Endocrine Abstracts

Background: 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. Furthermore, the role of NLRP3 inflammasome as an important trigger of inflammatory pathways and NLRP3 and CARD8 polymorphisms have never been addressed in PCOS yet.

Purpose: The aim of our study was to investigate genetic variability in the pathways associated with OS and inflammation and to assess their relationship with the risk of PCOS development as well as with metabolic characteristics in PCOS patients.

Methods: 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 (SOD2 rs4880, CAT rs10 01179, PON1 rs85 4560, and rs662) and inflammatory pathways genes (NLRP3 rs35 829419, CARD8 rs20 43211, TNFα rs18 00629, IL1β rs11 43623, and rs16 944, IL6 rs18 00795) using competitive allele-specific polymerase chain reaction (PCR). Logistic regression and Mann-Whitney test were used in the statistical analysis.

Results: SOD2 rs4880, CARD8 rs20 43211 and IL1 rs16944 were associated with the risk of developing PCOS. Furthermore, the interactions between CARD8 rs20 43211 and IL6 rs18 00795 and between IL1b rs11 43623 and IL6 rs18 00795 also significantly affected the risk for PCOS. With regards to glucose homeostasis, CAT rs10 01179, SOD2 rs4880, PON1 rs85 4560, NLRP3 rs35 829419, and TNFα rs18 00629 were significantly associated with response to the glycaemic load.

Conclusions: Our data indicates that genetic variability in antioxidative and inflammatory pathways influences the development of PCOS and glucose homeostasis in PCOS patients.