Association between CORIN promoter methylation and hypertensive disorders of pregnancy - A nested case-control study

Corin protein and its coding gene variants have been associated with hypertensive disorders of pregnancy (HDP), but the underlying mechanisms are unclear. As a mediator linking fixed genome with the dynamic environment, DNA methylation at the CORIN gene may link corin with HDP but not has been studied. This study aimed to examine whether CORIN promoter methylation and HDP in Chinese pregnant women.

Based on a cohort of Chinese pregnant women, we designed a nested case-control study including 196 cases with HDP and 200 healthy controls. DNA methylation levels in the CORIN promoter were quantified by pyrosequencing using peripheral blood before 20 gestational weeks. The association between DNA methylation in CORIN promoter and HDP was systemically examined by single CpG association analysis, followed by gene-based analysis. Multiple testing was controlled by the false discovery rate (FDR) method.

The single CpG association analysis found that, among the 5 CpG sites assayed, hypermethylation at one CpG site (Chr4:47839945) was significantly associated with HDP (OR = 1.94, raw P = 0.020), but the significance did not survive for multiple testing correction (FDR-P = 0.100). The gene-based association analysis found that DNA methylation of the 5 CpG sites was jointly associated with HDP (raw P = 0.003). In addition to HDP, CORIN promoter methylation was also significantly associated with dynamic blood pressure during pregnancy (raw P < 0.05).

Hypermethylation in CORIN promoter at early pregnancy was associated with the risk of HDP during late pregnancy in Chinese women. However, further evidence is required to establish the causality between CORIN promoter methylation and HDP.