LncRNA MEG3, GAS5, and HOTTIP Polymorphisms Association with Risk of Polycystic Ovary Syndrome: A Case-Control Study and Computational Analyses.

As a multifactorial and endocrine disease, polycystic ovary syndrome (PCOS) affects approximately 5-20% of women worldwide. Recently, long noncoding RNAs (lncRNAs) have emerged as potent predictors of a particular phenotype in PCOS. Our preliminary study examines the link between polymorphisms in lncRNAs MEG3, HOTTIP, and GAS5 and the risk of PCOS. The present study included 200 women with PCOS and 200 healthy women. The studied variations were genotyped by applying the PCR-RFLP and the tetra-ARMS-PCR reaction) techniques. The effect of variation in lncRNA on miRNA:lncRNA interactions, lncRNA-RNA interaction network, and the impact of the variations on the splicing site were predicted using different computational databases. The codominant heterozygous (TC vs. TT) model, the dominant (TC + CC vs. TT) model, the overdominant (TT + CC vs. TC) model, the C allele of rs2023843, and the C allele of rs55829688 had a protective role against PCOS. The A allele of rs4081134 and G allele of rs7158663 of the MEG3 conferred an increased risk of PCOS by 1.37 and 1.44 folds, respectively. The interaction analysis revealed that TC/GG/AA/TC and TC/GG/GA/TC strongly decreased the risk of PCOS by 94 and 92%, respectively. Interestingly, MEG3 and HOTTIP variants can create or disrupt binding sites for several splicing factors. In our population, MEG3 rs4081134 and rs7158663, GAS5 rs55829688, and HOTTIP rs2023843 polymorphisms were associated with PCOS risk. Replication studies on larger sample sizes must be conducted to confirm these findings and investigate other potential causative factors involved in the pathophysiology of PCOS.