Altered erythrocyte membrane protein composition mirrors pleiotropic effects of hypertension susceptibility genes and disease pathogenesis.
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 genes including ADD1 (rs4961), GNB3 (rs5443, rs16932941), NOS3 (rs1799983, rs2070744), ACE (rs5186), AGTR1 (rs5186), AGT (rs699, rs4762), MR (rs5534), 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.
aDepartment of Biology, Medical Genetics and Ecology, Kursk State Medical University bDivision of Cardiology, Kursk Regional Clinical Hospital, Kursk cDepartment of Medical Biological Disciplines, Belgorod State University, Belgorod dPopulation Genetics Laboratory, Research Institute for Medical Genetics, Tomsk, Russian Federation eDepartment of Physiology, Pathophysiology and Medical Biology, Sumy State University, Sumy, Ukraine.
Alexey V
AV
Polonikov
Dmitry V
DV
Ushachev
Vladimir P
VP
Ivanov
Mikhail I
MI
Churnosov
Maxim B
MB
Freidin
Alexander V
AV
Ataman
Victoria Yu
VY
Harbuzova
Marina A
MA
Bykanova
Olga Yu
OY
Bushueva
Maria A
MA
Solodilova
D000328:Adult; D002462:Cell Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D000075222:Essential Hypertension; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012727:Sex Characteristics
D008565:Membrane Proteins