Altered erythrocyte membrane protein composition mirrors pleiotropic effects of hypertension susceptibility genes and disease pathogenesis

Abstract

Objective:The study was designed to assess the effects of polymorphisms in genes associated with essential hypertension on the variation of erythrocyte membrane proteins (EMPs) in hypertensive patients. Methods:Major EMPs content was analyzed in blood from 1162 unrelated Russians (235 hypertensive patients, 176 healthy controls, and 751 random individuals from the Central Russia population). Essential hypertension patients were genotyped for 11 polymorphisms of essential hypertension susceptibility, and TGFB1 (rs1800471). EMP contents and their relationship with the genetic loci were analyzed using various statistical tests.Results: Sex-specific differences in EMP contents between the cases and controls were observed. Regardless of sex, hypertensives exhibited mainly decreased levels of alpha (SPTA1) and beta-spectrin (SPTB) and increased levels of glucose transporter (GLUT1) as compared with healthy subjects (P < 0.001). EMP correlated differently in essential hypertension patients and controls. Almost 70% of the joint variation in the EMP levels is explained by five gender-specific principal components. The essential hypertension susceptibility genes showed considerable effects on the levels of spectrins and glucose transporter. A joint variation of the genes explained about half the total polygenic variance in the GLUT1, SPTA1, and SPTB levels in hypertensives. Conclusions:The study showed that essential hypertension susceptibility genes are the important factors of the inherited EMP variation, and their pleitropic effects may be mirrored in the altered expression of genes encoding cytoskeletal proteins and those related to intracellular glucose metabolism.

An Ethnic Comparison of Arginine Dimethylation and Cardiometabolic Factors in Healthy Black and White Youth: The ASOS and African-PREDICT Studies

“…Major erythrocytic membrane proteins, which include spectrin-α, spectrin-β, ankyrin-1, and protein band 4.1, are Arg-dimethylated proteins [63]. Altered erythrocyte membrane protein composition has been shown to mirror the pleiotropic effects of hypertension susceptibility genes and disease pathogenesis [64]. The role of these Arg-dimethylated erythrocytic proteins in vascular function modulation is unknown.…”

A comprehensive study revealed SNP–SNP interactions and a sex-dependent relationship between polymorphisms of the CYP2J2 gene and hypertension risk

“…The discovery sample, including 1558 unrelated individuals (913 patients with EH and 645 age-and sex-matched healthy controls), was recruited from the Cardiology Clinics of Kursk Regional Clinical Hospital and the Neurology Clinics of Kursk Emergency Medicine Hospital. These study patients were enrolled during two study periods: the first period was between 2003 and 2006 and the second period was between 2007 and 2012 [34][35][36][37]. The control group included blood donors, healthy volunteers and hospital-based patients (all subjects were recruited from the surgical, traumatic, and infectious divisions of Kursk hos pitals) with normal blood pressure and without cardiovas cular or other chronic diseases.…”

“…The control group included blood donors, healthy volunteers and hospital-based patients (all subjects were recruited from the surgical, traumatic, and infectious divisions of Kursk hos pitals) with normal blood pressure and without cardiovas cular or other chronic diseases. The control group was recruited over the same periods of time [34][35][36][37][38]. To ensure an ethnically homogeneous population, only Russian resi dents living in Central Russia for at least two generations have been included in the study.…”

A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

“…The study protocol was approved by the Ethical Review Committee of Kursk State Medical University and written informed consent was obtained from each participant before enrollment. A total of 2160 unrelated individuals of Russian origin from of the Central Russia (predominantly from Kursk region) comprising 1341 EH patients and 819 healthy individuals with normal BP were recruited at Cardiology Clinics of Kursk Regional Clinical Hospital and Neurology Clinics of Kursk Emergency Medicine Hospital as described previously [49,50]. EH was diagnosed by qualified cardiologists.…”