Genetic polymorphism in DGCR8 is associated with late onset of preeclampsia
Genetic polymorphism in DGCR8 is associated with late onset of preeclampsia
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DGCR8 基因多态性与先兆子痫迟发型相关
DOI：
10.1186/s12881-019-0887-7
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发表时间：
2019-09-04
影响因子：
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通讯作者：
Zhang, Yujing
中科院分区：
文献类型：
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作者：
Huang, Xin;Li, Zuodong;Zhang, Yujing
背景PE（先兆子痫）是一种异质性疾病，具有早发性PE（EOPE）和晚发性PE（LOPE）亚型。先前已观察到母体 miRNA 生物合成基因多态性与 PE 风险之间的关联。然而，DGCR8 的多态性（在 miRNA 成熟过程中必不可少）对先兆子痫 (PE) 易感性的影响尚未阐明。因此，我们进行了一项病例对照研究，以评估 DGCR8 多态性对 EOPE 和 LOPE 风险的影响。方法总共招募了 66 名诊断为 EOPE 的患者、206 名 LOPE 患者和 330 名健康对照者。对 DGCR8 中的 5 个 SNP 进行了基因分型，包括 rs1558496、rs1640299、rs720012、rs720014 和 rs9606241。使用逻辑回归来估计相关性的 OR 和 95% CI。 结果在 rs1640299 TG 基因型（OR = 1.98 (95%CI: 1.38, 2.87), p = 2.32e-4）和 rs720014 TC 基因型患者中观察到 LOPE 风险增加(OR = 2.49 (95%CI: 1.72, 3.60), p = 1.40e-7)。 DGCR8 rs1558496/ rs1640299/ rs720012/ rs720014/ rs9606241 单倍型 T-G-A-C-A 和 T-G-A-C-G 与 LOPE 风险增加相关（OR = 2.20 (95%CI: 1.49, 3.25)， p = 5.90e-5 和 1.58（95%CI：1.06、2.36），p = 0.024。单倍型 T-T-G-T-A 与较低的 LOPE 风险相关（OR = 0.74 (95%CI: 0.58, 0.95), p = 0.018）。在假阳性发现率校正后，这些显着的关联仍然存在。但所检测的DGCR8基因SNPs或单倍型均与EOPE风险无关(p≥0.05)。结论DGCR8基因多态性可能参与了子痫前期的病理过程。 rs1640299 T > G 和 rs720014 T > C 多态性与晚发性先兆子痫易感性相关。
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.