Low-dose aspirin is widely prescribed in pregnancy to prevent preeclampsia and related complications. However, a significant proportion of women experience adverse outcomes despite aspirin use, suggesting potential resistance mechanisms. Emerging evidence points to the importance of inflammatory pathways, particularly involving the COX-2 enzyme (encoded by PTGS2), in modulating aspirin’s efficacy.
This project aims to explore whether genetic variants in the PTGS2 gene and related inflammatory biomarkers are associated with poor pregnancy outcomes in women who used aspirin during pregnancy. Specifically, we will:
1. Identify women in the UK Biobank cohort with records of aspirin use and pregnancy history.
2. Compare the incidence of adverse outcomes (e.g., preeclampsia, fetal growth restriction, preterm birth) among women with and without key PTGS2 variants (e.g., rs20417, rs5275).
3. Investigate whether inflammatory markers (e.g., CRP) or comorbidities (e.g., high BMI, hypertension) modify the relationship between genotype and outcome.
4. Use statistical modelling to assess whether PTGS2 SNPs and biomarkers can help identify women at risk of aspirin resistance.
This pilot study will provide a genetic and biomarker-based framework for understanding aspirin non-response in pregnancy. The findings will inform future mechanistic studies using primary placental and immune cells, and ultimately contribute to personalised approaches for preventing pregnancy complications.