P36. Identifying a novel link between preeclampsia and chronic hypertension in the MTHFR-gene using the population based Norwegian HUNT Study

Introduction Preeclampsia is a complex genetic disease of pregnancy including new-onset hypertension with proteinuria. Research has demonstrated that after preeclamptic pregnancies these women are at increased risk for cardiovascular diseases (CVD) later in life. Although the link between the diseases is currently obscure, the pathophysiology of both conditions incorporates dysregulated inflammation. Objectives In this study we aimed to identify genetic components of the shared pathophysiology of preeclampsia and the CVD risk factor chronic hypertension. Methods A cohort from the Norwegian HUNT Study was selected, containing 1006 women with a history of preeclampsia and 816 women with non-preeclamptic pregnancies. From significant findings in existing genome-wide association studies on either chronic hypertension or inflammation we identified 122 candidate single nucleotide polymorphisms (SNPs). These SNPs were genotyped on the Sequenom MassArray System and tested for association with preeclampsia and chronic hypertension in the selected HUNT Study cohort in a multiple logistic regression model in PLINK software. Results After Bonferroni-adjustment the minor allele of the intronic SNP rs17367504 in the methylenetetrahydrofolate reductase (MTHFR) gene was significantly associated with a protective effect on preeclampsia (minor allele frequency 13%, OR 0.65, CI 95% 0.53–0.80, p  = 3.52 × 10 −5 ). This SNP did not demonstrate a significant association with chronic hypertension in our data set. Conclusion Our study demonstrates a genetic link between PE and CVD. The MTHFR enzyme has been linked repeatedly to the regulation of folic acid while the minor allele of the MTHFR SNP rs17367504 is known to be associated with a protective effect on chronic hypertension in CVD-based cohorts. We have identified a novel effect of the MTHFR SNP rs17367504, finding this SNP to be associated with reduced risk of preeclampsia.