Genetic Associations with Polycystic Ovary Syndrome: The Role of The Mitochondrial Genome; A Systematic Review and Meta-analysis

BACKGROUND: Polycystic Ovary Syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, whilst the contribution of mitochondrial genetics in PCOS remains largely unknown. AIM: This study aims to systematically evaluate the literature regarding the associations between the mitochondrial genome and PCOS. METHODS: A literature search focused on PCOS and mitochondrial genetics was conducted on (1) MEDLINE (2) EMBASE and (3) The Cochrane Library (CENTRAL and Cochrane Reviews). Search results were screened for eligibility, and data involving genetic variants of mitochondrial DNA (mtDNA) was extracted. Quantitative data was presented in forest plots, and where this was not possible, data was analysed in a qualitative manner. Quality of studies was assessed using the Q-Genie tool. RESULTS: Of the 13,812 identified studies, 15 studies were eligible for inclusion, with 8 studies suitable for meta-analysis. Women with PCOS showed higher frequencies of a 9-bp deletion, and aberrant SNPs in the ND5, A6, and 7 tRNA-encoding genes. They also showed lower frequencies of two SNPs in the D-Loop of the genome. Women with PCOS also exhibited significantly lowered mtDNA copy number. CONCLUSION: Women with PCOS harbour genetic variants in coding and non-coding regions of the mitochondrial genome. This may disrupt the electron transport chain and lead to oxidative stress, causing apoptosis of cells and further genetic damage. However, further studies of higher quality are required to confirm these associations