Preeclampsia and Keap1 (rs11085735) variants and lncRNA MEG3 methylation status: Association with lncRNA MEG3 hypermethylation

Abstract Background. Preeclampsia (PE) is one of the complications of pregnancy. Genetic and epigenetic mechanisms are involved in the preeclampsia pathophysiology. The aims of present study were to investigate the role of Keap1 (rs11085735) variants and the methylation status of long non-coding RNA-maternally expressed gene 3 (lncRNA MEG3) in the pathogenesis of PE in a population from Western Iran with Kurdish ethnic background.Results. There was no significant difference in the frequency of Keap1 genotypes comparing 75 patients with PE and 75 women with normal pregnancy. The frequencies of hemi methylated and full methylated lnc-MEG3 were 94 and 6% (P=0.04), respectively in all patients (50 women), 86.4, and 13.6% (P=0.04), respectively in patients with severe preeclampsia and 98 and 0% in controls (50 women). The frequency of full methylated lnc-MEG3 was 14.3% in early-onset and 2.8% in late-onset preeclampsia (P=0.12). The frequency of full methylated lnc-MEG3 was higher in patients with BMI >25 kg/m2 compared to normal weight patients. The PE patients had significantly higher levels of liver biomarkers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin) and significantly lower platelet count than healthy pregnant women. Conclusions. Hypermethylation status of lnc-MEG3 increased in patients with PE compared to controls that could be contributed in the pathogenesis and development of preeclampsia and its severe form. However, Keap1 variants might not be involved in the pathogenesis of preeclampsia.