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

ABSTRACT: 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.

SUBMITTER: Huang X

PROVIDER: S-EPMC6727569 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Huang Xin X Li Zuodong Z Lei Jun J Wang Dapeng D Zhang Yujing Y

BMC medical genetics 20190904 1

<h4>Background</h4>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 i ...[more]

PMID: 31484500

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Project description:Hypertension in pregnancy is the leading cause of morbidity and mortality in pregnancy, affecting up to 10% of all gestations1. Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, eclampsia and pre-eclampsia, all of which increase the risk of complications in both mothers and babies during gestation. Preeclampsia, in particular, is characterised by the new-onset of gestational hypertension in the presence of proteinuria or other organ damage. It affects 5-7% of pregnancies and causes approximately 76,000 maternal deaths and 500,000 foetal deaths worldwide each year2. The classification of preeclampsia has been evolving over the last decade. In 2013, American College of Obstetricians and Gynecologists (ACOG) and International Society for the Study of Hypertension in Pregnancy (ISSHP) in the absence of proteinuria included other symptoms/features including liver dysfunction, thrombocytopenia, cerebrovascular events or foetal growth restriction (FGR) in the diagnosis of preeclampsia 1,3,4. Despite the fact that preeclampsia is a multifactorial and heterogeneous disorder, it is now widely accepted that preeclampsia is stratified depending on the time of onset into: i) early-onset PE (EOPE) manifested before 34 weeks of gestation, and ii) late-onset PE (LOPE) manifested from 34 weeks of gestation. Although EOPE and LOPE share the same diagnostic criteria, these two phenotypes of preeclampsia lead to different outcomes. EOPE is commonly associated with FGR, abnormal uterine artery Doppler often leading to preterm birth and higher risk of post-pregnancy morbidities5,6. On the other hand, LOPE appears to be a less severe disorder, often with normal or slightly increased uterine resistance index and a low rate of FGR6,7. Distinct delineation between EOPE and LOPE is still not well understood, with most patients with preeclampsia presenting elements of both pathologies proposing a clinical spectrum for preeclampsia. The lack of untargeted discovery studies involving ‘omics’ analyses has impeded understanding of the molecular differences between these two phenotypes of preeclampsia. Notably, a study from 20058 utilised a proteomics approach using urine samples from a cohort of pregnant women with EOPE and healthy controls, however the differences between EOPE and LOPE were not elucidated. Another more recent bioinformatics study, identified overlapping pathogenic mechanisms between preeclampsia, hypertension and heart disease but could not stratify between EOPE and LOPE due to underreported of data related to individual phenotypes9. In this study, we conducted an unbiased, comprehensive proteomics investigation using plasma samples collected from patients with EOPE (n=17) and LOPE (n=11), compared with age- and BMI-matched normotensive controls (n=18). The use of plasma samples is able to better reflect the pathogenesis of EOPE and LOPE as systemic conditions centred by widespread endothelial dysfunction.

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

Publications

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

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