Association between risk of preeclampsia and maternal plasma trimethylamine-N-oxide in second trimester and at the time of delivery.

BACKGROUND: The data on the association between the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) during pregnancy and risk of preeclampsia (PE) is limited. METHODS: We, therefore, conducted a prospective nested case control study during Sep 2017 to Dec 2018 to examine the association between plasma TMAO measured during pregnancy and the risk of PE. Total of 17 patients diagnosed with early onset PE (EOPE), 49 with late onset PE (LOPE) and 198 healthy controls were enrolled. Blood samples were collected at 15-23 weeks gestation and time at delivery. The Logistic regression model was used to assess the odds ratio (OR) and 95% confidence interval (CI) for TMAO and risk of PE, EOPE, LOPE, mild PE, and severe PE. RESULTS: We found that the mean TMAO levels of overall subjects in the second trimester (T2) and at the time of delivery (TD) were 90.39 µg/m3 (standard deviation (SD) =45.91) and 175.01 µg/m3 (SD = 160.97), respectively. No significant spearman correlation was found between the TMAO in those two periods (p > 0.05). T2 TMAO was not significantly associated with risk of PE or risk of any PE subtypes (p > 0.05). However, TD TMAO was significant associated with risk of PE, EOPE and severe PE (adjusted OR and 95%CI were 1.24(1.09, 1.40), 1.62(1.29, 2.03), and 1.41(1.17, 1.70)) per 50 µg/m3 increment, respectively). CONCLUSION: Our study found that plasma TMAO level would alter over the course of pregnancy. The major role of TMAO in PE development might be in the accelerating process not in the initiation.

Genetic polymorphism in DGCR8 is associated with late onset of preeclampsia.

BACKGROUND: PE (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. METHODS: A 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. RESULTS: Increased 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). CONCLUSIONS: Polymorphisms 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.