Association of Keap1 (rs11085735) polymorphism and lncRNA MEG3 hypermethylation status with the risk of preeclampsia

Abstract

Abstract Background Preeclampsia (PE) is one of the complications of pregnancy. The pathogenesis of PE has not been completely understood. The aims of the present study were to investigate the role of Keap1 (rs11085735) variants and the methylation status of long non-coding RNA (lncRNA) MEG3 in the risk of PE. Methods In a case–control study, 150 pregnant women, including 75 PE patients and 75 healthy pregnant women recruited from Western Iran with Kurdish ethnic background, were studied for Keap1 variants using polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP). The methylation status of lncRNA MEG3 was investigated using methylation-specific PCR (MSP) among 50 preeclamptic patients and 50 controls. Results The frequency of Keap1 A allele was significantly lower (5.3%) in preeclamptic patients compared to controls (12.7%, p = 0.024). The frequencies of hemimethylated (UM) and full methylated (MM) lncRNA MEG3 were 94 and 6% (p = 0.04), respectively, in all patients, 86.4, and 13.6% (p = 0.04), respectively, in patients with severe preeclampsia and 98 and 0% in controls. The frequency of full methylated lncRNA MEG3 was 14.3% in early-onset preeclampsia and 2.8% in late-onset preeclampsia (p = 0.12). Patients with PE had significantly higher levels of liver biomarkers (including ALT, AST, ALP, and total bilirubin) and lower PLT counts compared to healthy pregnant women. Conclusion The present study suggests the presence of hypermethylation status of lncRNA MEG3 in preeclampsia that might contribute to the pathogenesis and development of preeclampsia. Also, Keap1 rs11085735 polymorphism might be involved in the risk of preeclampsia.

Keywords

• Preeclampsia
• Keap1 (rs11085735)
• lncRNA MEG3
• Methylation
• Western Iran