Abstract
BackgroundPE (preeclampsia) is a heterogeneous disorder with early onset PE (EOPE) and late onset PE (LOPE) subtypes. Associations between maternal miRNAs biosynthesis genes polymorphisms and risk of PE have been previously observed. However, the impact of polymorphisms in DGCR8 which is indispensable in miRNA maturing processing on the susceptibility to preeclampsia (PE) has not been elucidated yet. We, therefore, conducted a case-control study to evaluate the impact of polymorphisms in DGCR8 on the risk of EOPE and LOPE.MethodsA total of 66 patients diagnosed with EOPE, 206 with LOPE and 330 healthy controls were recruited. Five SNPs in DGCR8 were genotyped including rs1558496, rs1640299, rs720012, rs720014, and rs9606241. Logistic regression was used to estimate the OR and the 95% CI for the associations.ResultsIncreased risk of LOPE has been observed among patients with rs1640299 TG genotype (OR = 1.98 (95%CI: 1.38, 2.87), p = 2.32e-4) and rs720014 TC genotype (OR = 2.49 (95%CI: 1.72, 3.60), p = 1.40e-7). The DGCR8 rs1558496/ rs1640299/ rs720012/ rs720014/ rs9606241 haplotype T-G-A-C-A and T-G-A-C-G were associated with increased risk of LOPE (OR = 2.20 (95%CI: 1.49, 3.25), p = 5.90e-5, and 1.58 (95%CI: 1.06, 2.36), p = 0.024, respectively). And the haplotype T-T-G-T-A was associated with lower risk of LOPE (OR = 0.74 (95%CI: 0.58, 0.95), p = 0.018). These significant associations retained after false-positive discovery rate correction. However, none of the tested SNPs or haplotypes in DGCR8 gene is associated with risk of EOPE (p > 0.05).ConclusionsPolymorphisms in DGCR8 might participate in the pathological process of preeclampsia. The rs1640299 T > G and rs720014 T > C polymorphisms are associated with late onset preeclampsia susceptibility.
Highlights
PE complicates 2–5% of pregnancies and is a major cause of maternal, fetal, and neonatal morbidity and mortality [1]
Both Early onset preeclampsia (EOPE) and late onset PE (LOPE) cases were older than controls
No significant differences in the distribution of maternal education, or fetal gender were found between EOPE, LOPE and controls
Summary
PE (preeclampsia) complicates 2–5% of pregnancies and is a major cause of maternal, fetal, and neonatal morbidity and mortality [1]. The biosynthesis of miRNAs is a tightly regulated multistep process. Single nucleotide polymorphisms (SNPs) within those miRNAs biosynthesis genes can result in DiGeorge critical region 8 (DGCR8) is an RNA binding protein which interacts with Drosha to produce premicroRNA in the nucleus and is indispensable in miRNA maturing processing [9]. The impact of polymorphisms in DGCR8 on the susceptibility to PE has not been elucidated. Associations between maternal miRNAs biosynthesis genes polymorphisms and risk of PE have been previously observed. The impact of polymorphisms in DGCR8 which is indispensable in miRNA maturing processing on the susceptibility to preeclampsia (PE) has not been elucidated yet. We conducted a casecontrol study to evaluate the impact of polymorphisms in DGCR8 on the risk of EOPE and LOPE
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