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DICER1、DROSHA、RAN 和 XPO5 基因中的遗传变异与妊娠高血压的风险。

Genetic variants in DICER1, DROSHA, RAN, and XPO5 genes and risk of pregnancy-induced hypertension.

机构信息

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

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

出版信息

Pregnancy Hypertens. 2019 Apr;16:161-166. doi: 10.1016/j.preghy.2019.04.005. Epub 2019 Apr 16.

DOI:10.1016/j.preghy.2019.04.005
PMID:31056154
Abstract

OBJECTIVE

To evaluate the impact of microRNA (miRNA) machinery gene polymorphisms on the risk of gestational hypertension (GH) and preeclampsia (PE).

STUDY DESIGN

A case-control study among Han Chinese with a total of 143 patients diagnosed with PE, 79 with GH, and 330 healthy controls was conducted. Nine candidate SNPs in 4 selected miRNA biogenesis genes were genotyped, including three DICER1 SNPs (rs3742330, rs1057035 and rs13078), two DROSHA SNPs (rs17409893 and rs642321), two RAN SNPs (rs3803012 and rs14035), and two XPO5 SNPs (rs1106841 and rs2257082). Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for the associations.

RESULTS

The DICER1 rs13078 TA genotype was still strongly associated with an increased risk of GH (OR = 3.17 (95% CI: 1.55, 6.48)), and the RAN rs3803012 AG genotype was associated with an increased risk of PE (OR = 2.15 (1.26, 3.66)). The RAN rs14035/rs3803012 haplotype C-G was associated with PE susceptibility (OR = 2.08 (95% CI: 1.19, 3.62)); however, the haplotype C-A was a protective factor for PE (OR = 0.68 (95% CI: 0.50, 0.93)). The DICER1 rs1057035/ rs13078/ rs3742330 haplotype T-A-A and DORSHA rs17409893/rs642321 haplotype A-T were both associated with increased risk of GH (OR = 2.75 (95% CI:1.40, 5.38) and OR = 1.60 (95% CI:1.12, 2.29), respectively). These significant associations were retained after false-positive discovery rate correction (p < 0.05).

CONCLUSIONS

Genetic variants in miRNA machinery genes might participate in the development of pregnancy-induced hypertension. The DICER1 rs1078 polymorphism is associated with GH and the RAN rs3803012 polymorphism is associated with PE.

摘要

目的

评估微小 RNA (miRNA) 机制基因多态性对妊娠期高血压 (GH) 和子痫前期 (PE) 风险的影响。

研究设计

这是一项在中国汉族人群中进行的病例对照研究,共纳入 143 例 PE 患者、79 例 GH 患者和 330 例健康对照者。对 4 个选定的 miRNA 生物发生基因中的 9 个候选单核苷酸多态性 (SNP) 进行了基因分型,包括三个 DICER1 SNP(rs3742330、rs1057035 和 rs13078)、两个 DROSHA SNP(rs17409893 和 rs642321)、两个 RAN SNP(rs3803012 和 rs14035)和两个 XPO5 SNP(rs1106841 和 rs2257082)。采用 logistic 回归估计关联的优势比 (OR) 和 95%置信区间 (CI)。

结果

DICER1 rs13078 TA 基因型与 GH 风险增加仍密切相关 (OR=3.17(95%CI:1.55, 6.48)),RAN rs3803012 AG 基因型与 PE 风险增加相关 (OR=2.15(1.26, 3.66))。RAN rs14035/rs3803012 单倍型 C-G 与 PE 易感性相关 (OR=2.08(95%CI:1.19, 3.62));然而,单倍型 C-A 是 PE 的保护因素 (OR=0.68(95%CI:0.50, 0.93))。DICER1 rs1057035/rs13078/rs3742330 单倍型 T-A-A 和 DORSHA rs17409893/rs642321 单倍型 A-T 均与 GH 风险增加相关 (OR=2.75(95%CI:1.40, 5.38)和 OR=1.60(95%CI:1.12, 2.29),均 P<0.05)。经假阳性发现率校正后,这些显著关联仍然存在 (P<0.05)。

结论

miRNA 机制基因中的遗传变异可能参与妊娠相关性高血压的发生。DICER1 rs1078 多态性与 GH 相关,RAN rs3803012 多态性与 PE 相关。

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