Variants in the 5'-UTR of APELA gene in women with preeclampsia.

ABSTRACT

OBJECTIVE: To detect APELA gene variants in clinical cases with preeclampsia (PE) and evaluate the influence of the APELA variants in gene expression. METHOD: A total of 288 individuals suffering from PE and 384 unaffected individuals were chosen for case-control studies. Genomic DNA was extracted from peripheral blood. Variants screening of APELA gene was conducted, and potential influence of variants in APELA expression was evaluated with a luciferase assay. RESULTS: Two rare variants (c.-306A > G and c.-145A > G) in the 5'-UTR of APELA gene were identified exclusively in PE affected individuals. Luciferase assays in HEK293 cells and HTR-8/SVneo cells revealed that both variants impaired transcriptional activity of APELA by altering the function of promoter region. Also, a single-nucleotide polymorphism (SNP) (c.159 T > C) in exon 2 of APELA was found in both cases and controls, and there was no statistically significant difference in genotype and allele frequency between cases and controls. CONCLUSION: Variants in the 5'-UTR of APELA gene may account for variability of APELA expression among individuals with PE and may play a negative regulatory role in the pathogenesis of PE.