Associations of MicroRNA Polymorphisms (miR-146a, miR-196a2, and miR-499) with the Risk of Hypertension in the Korean Population

Aims: Polymorphisms in microRNA (miR) genes are thought to be associated with various cancers and vascular diseases. To date, however, the effects of the miR gene polymorphisms on susceptibility to hypertension have rarely been investigated. In this study, we investigated the associations of three miR gene polymorphisms (miR-146aC>G/rs2910164, miR-196a2T>CIrs11614913, and miR-499A>G/rs3746444) with the risk of hypertension in Korean patients. Methods: A total of 855 study subjects (340 patients with hypertension and 515 healthy normotensive subjects) were included in this study. Genotyping of the three miR gene polymorphisms was accomplished by polymerase chain reaction restriction fragment length polymorphism analyses. Results: Significant differences were observed in the genotype distributions of the miR-146aC>G polymorphism between the hypertensive patients and controls with the GG genotype, in both model-independent analyses, as well as in dominant (CC vs. CG+GG) and recessive (CC+CG vs. GG) models, being highly significantly associated with disease (AOR = 2.293, 95% CI: 1.466-3.586, p = 0.001; AOR = 1.727, 95% CI: 1.182-2.522, p = 0.015; AOR = 1.782, 95% CI: 1.267-2.506, p = 0.001, respectively). Neither the miR-196a2T>C nor the miR-499A>G polymorphisms were distributed significantly differently between hypertensive patients and control subjects. Several allelic combinations of the three miR polymorphisms were also associated with susceptibility to hypertension. Stratified analysis revealed that the miR-146aC>G and miR-499A>G polymorphisms are associated with a greater risk of hypertension. Conclusion: This study suggests that the variant of miR-146aC>G polymorphism and allelic combinations, at least in Koreans, affect susceptibility to hypertension.