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

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.