Genetic associations of miR-145 (rs353291) and miR-143/145 (rs3733846) with preeclampsia risk: a case-control analysis in maternal and cord blood

Abstract

Preeclampsia (PE), affecting 1-5% of pregnancies, is a major cause of maternal and neonatal morbidity. Dysregulated microRNAs, especially miR-145 and the miR-143/145 cluster, contribute to PE via placental and vascular dysfunction. This study examined the rs353291 and rs3733846 polymorphisms in maternal and cord blood to assess PE susceptibility in Iranians. A case-control study was conducted with 320 maternal samples (160 PE, 160 controls) and 202 cord samples (101 PE, 101 controls). PE was diagnosed according to the ACOG of Obstetrics and Gynecology criteria (≥ 140/90 mmHg after 20 weeks of proteinuria). Genomic DNA from maternal and cord blood was genotyped for rs353291 and rs3733846 using tetra-primer ARMS-PCR and confirmed by Sanger sequencing. Associations tested in SNPStats under codominant, dominant, recessive, overdominant, and log-additive models. In cord blood, the rs353291 G allele frequency was higher in PE (43% vs. 32%, p < 0.05), with the homozygous G/G genotype conferring a threefold increased risk (OR = 3.31, p = 0.032). Conversely, rs3733846 A/G heterozygosity reduced the PE risk (OR = 0.24, p = 0.0002). In the maternal blood, rs353291 A allele carriers showed an elevated risk (OR = 1.66, p = 0.025), while rs3733846 exhibited no association. Maternal and fetal miR-145 and miR-143-145 polymorphisms had distinct effects on PE. Cord rs353291 G is linked to placental and fetal vascular dysfunction, maternal rs353291 A is linked to systemic inflammation, and cord rs3733846 A/G appears to be protective. These findings suggest the potential of these variants as biomarkers for PE risk; however, further validation in larger, multi-ethnic cohorts is required before clinical application.

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Affiliated Institutions

• Shahid Beheshti University IR
• Iran University of Medical Sciences IR
• Islamic Azad University Medical Branch of Tehran IR
• Sarem Cell Research Center IR
• University of Social Welfare and Rehabilitation Sciences IR
• Islamic Azad University, Tehran IR
• Tehran University of Medical Sciences IR

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