Relationship between hysterectomy and global DNA methylation levels in peripheral blood: an exploratory follow-up study

Objective: The present study aims to understand the relationship between hysterectomy and peripheral blood leukocyte (PBL) global DNA methylation independently and in light of selected biochemicals (vitamin B12, folate, homocysteine). Material and methods: For the present population-based follow-up study, a total of 616 women aged 30–70 years were recruited from Haryana, India. Recruited participants underwent a baseline assessment, which included the determination of menopausal and hysterectomy status and estimation of vitamin B12, folate, homocysteine, and PBL global DNA methylation (5mC) levels. The 5mC levels were analyzed using ELISA-based colorimetric technique. Participants with no history of hysterectomy were followed up after 8 years, and their current menopausal and hysterectomy statuses were determined. Result: The median PBL 5mC level of the group with hysterectomy was found to be significantly lower than that of those without hysterectomy in the baseline assessment (PBL 5mC = 0.47 vs. 0.74, respectively; p-value = 0.016). However, there was no significant difference in baseline median PBL 5mC levels between women who eventually underwent hysterectomy and those who did not. When stratified for biochemical levels, the trend of PBL global DNA hypomethylation in the hysterectomy group, compared to the no-hysterectomy group, was statistically significant only within the normal folate group. Conclusion: This study suggests a potential association between hysterectomy (or related factors) and global DNA hypomethylation. Further research is warranted to validate the findings of the present study and to advance the existing knowledge regarding the epigenetic implications of hysterectomy.