Associations of leptin receptors and miRNA polymorphisms with susceptibility to hypertension.

Abstract

Leptin receptors (LEPR) are located in the central nervous system and other tissues including adipocytes and endothelial cells, where they play a key role in mediating the effects of leptin. MicroRNA (miR/miRNA)-27a and miR-155 have been shown to play an important role in the regulation of LEPR expression and are differentially expressed in various diseases. Therefore, the present study analyzed potential associations of LEPR deletion/insertion (Del/Ins), miR-27aA>G (rs895819) and miR-155T>A (rs767649) polymorphisms with a predisposition to hypertension (HTN). Genotyping was performed by a PCR-restriction fragment length polymorphism assay. Frequencies of LEPR Del/Ins and miRNA gene polymorphisms in patients diagnosed with HTN (n=232) and randomly selected healthy controls (n=247) were assessed. The present study found that Del/Ins and Ins/Ins genotypes and the Ins allele of the LEPR Del/Ins polymorphism were associated with a decreased risk of HTN compared with controls, whereas the miR-27aA>G rs895819 polymorphism was associated with an increased risk of HTN. Combined genotype and allele analyses for LEPR Del/Ins and two miRNA polymorphisms revealed an association with an increased risk or a decreased risk of HTN. Furthermore, stratification analysis revealed that HTN risk factors were associated with waist circumference (WC) and high-density lipoprotein cholesterol (HDL-C) values in LEPR Del/Ins polymorphism. They were also associated with body mass index, WC, triglyceride and HDL-C values in miR-27aA>G polymorphism. The present study revealed a combined effect of LEPR Del/Ins and miR-27aA>G polymorphisms on the risk of HTN in Koreans, suggesting that these gene polymorphisms could be potential markers for predicting HTN risk.