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DGCR8 基因多态性与子痫前期发病时间晚相关。

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

机构信息

Department of Preventive Medicine, School of Medicine, Hunan Normal University, 371 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China.

Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.

出版信息

BMC Med Genet. 2019 Sep 4;20(1):151. doi: 10.1186/s12881-019-0887-7.

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.

摘要

背景

PE(子痫前期)是一种具有早发型 PE(EOPE)和晚发型 PE(LOPE)亚型的异质性疾病。先前观察到母体 miRNA 生物合成基因多态性与 PE 风险之间存在关联。然而,miRNA 成熟加工所必需的 DGCR8 基因多态性对子痫前期(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

共纳入 66 例 EOPE 患者、206 例 LOPE 患者和 330 例健康对照者。对 DGCR8 中的 5 个 SNPs(rs1558496、rs1640299、rs720012、rs720014 和 rs9606241)进行基因分型。使用 logistic 回归估计关联的 OR 和 95%CI。

结果

与 rs1640299TG 基因型(OR=1.98(95%CI:1.38,2.87),p=2.32e-4)和 rs720014TC 基因型(OR=2.49(95%CI:1.72,3.60))相比,LOPE 患者的 LOPE 风险增加,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)。与 LOPE 风险降低相关的单倍型 T-T-G-T-A(OR=0.74(95%CI:0.58,0.95),p=0.018)。这些显著的关联在经过假阳性发现率校正后仍然存在。然而,DGCR8 基因中的任何测试 SNP 或单倍型均与 EOPE 风险无关(p>0.05)。

结论

DGCR8 多态性可能参与子痫前期的病理过程。rs1640299T>G 和 rs720014T>C 多态性与晚发型子痫前期易感性相关。

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