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An miR-143 promoter variant associated with essential hypertension.

ABSTRACT: MicroRNAs like miR-143 are increasingly linked to disease pathogenesis. miR-143 is enriched in vascular smooth muscle, and several single nucleotide polymorphisms have been identified in this miRNA. The aim of the current study was to explore a potential correlation between a polymorphism in the miR-143 promoter region, rs4705342, and essential hypertension (EH). Genotyping for miR-143 rs4705342 was performed from blood samples of 156 EH patients (case group) and 187 healthy individuals (control group) using a TaqMan assay. Participant demographic and clinical characteristics were also collected. Logistic regression was used to identify an association between genotype and EH, and odds ratios of EH risk were also determined. Frequencies of the CC, CT, and TT genotypes differed significantly between case (7.7%, 40.4%, 51.9%) and control (15.0%, 48.1%, 36.9%) groups (?(2) = 9.400, P = 0.009). Further, the frequency of the C allele was lower in the case group than in the control group (27.9% vs. 39.0%, P = 0.002). Compared with those having the TT genotype, patients carrying the CC and CT genotypes had a significantly reduced risk for EH (OR = 0.541, 95% CI = 0.351-0.834, P = 0.005), particularly for females, nonsmokers, and those not consuming alcohol (P < 0.05). Thus, the rs4705342 polymorphism in the miR-143 appears to be associated with essential hypertension, and further study is needed to understand the molecular mechanism producing this effect.

SUBMITTER: Fu X

PROVIDER: S-EPMC4132149 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Project description:BackgroundAn elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients.MethodsA total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson's correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients.ResultsMiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects.ConclusionThe results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.

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An miR-143 promoter variant associated with essential hypertension.

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