Association study to evaluate Foxo1 and Foxo3 gene polymorphisms in polycystic ovary syndrome: a preliminary case–control study and in silico analysis

• Published in: Molecular biology reports 2023-04, Vol.50 (4), p.3569-3580
• Main Authors: Rakhshani Nejad, Arghavan, Sargazi, Saman, Ghasemi, Marzieh, Samareh Moosavi, Saeedeh, Heidari Nia, Milad, Saravani, Ramin
• Format: Article
• Language: English
• Subjects: Alleles; Animal Anatomy; Animal Biochemistry; Bioinformatics; Biomedical and Life Sciences; Case-Control Studies; Endocrine disorders; Female; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O3 - genetics; Forkhead protein; FOXO1 protein; FOXO3 protein; Gelatinase B; Gene polymorphism; Genetic Predisposition to Disease; Genotyping; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 - genetics; Histology; Humans; Iran; Life Sciences; Metabolic disorders; Metalloproteinase; Morphology; Original Article; Ovaries; Peroxisome proliferator-activated receptors; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polymerase chain reaction; Polymorphism, Single Nucleotide - genetics; Population studies; Transcription factors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08292-w

Background Polycystic ovary syndrome (PCOS) is known as a multifactorial and multi-gene-mediated endocrine disorder among women of reproductive age. FoxO1 and FoxO3 are members of the forkhead transcriptional factors family that play a pivotal role in the function of ovaries. The current work is aimed at investigating the association between gene variants of FoxO1 and FoxO3 and the risk of PCOS in a sample of the Iranian population. Methods and results We recruited 200 women diagnosed with PCOS and 200 healthy women. Both polymerase PCR–RFLP and ARMS-PCR methods were used for genotyping. Sanger sequencing was recruited to confirm the genotyping results. The T allele of rs17592236 and the C allele of rs12585277 decreased PCOS risk by 29 and 28%, respectively. In contrast, the C allele of rs2253310 and G allele of rs2802292 increased the risk of PCOS by 1.39 and 1.63 folds, correspondingly. Bioinformatics results showed that some genes, including matrix metallopeptidase 9 (MMP-9) , phosphoinositide-3-Kinase Regulatory Subunit 224 1 (PIK3R1) , peroxisome proliferator-activated receptor Gamma (PPARG) , and glycogen synthase 225 kinase-3 beta (GSK-3 beta) have significant interactions with FoxO1, suggesting that FoxO1 might have crucial roles in regulating different signaling pathways in ovarian cells . Conclusion We found that FoxO1 rs17592236C > T and rs12585277C > T had a protective role against PCOS, while FoxO3 rs2253310C > G and rs2802292G > T  enhanced the risk of this metabolic disorder in our population. Additional studies on larger populations with varying races are needed to confirm these findings. Graphical abstract