ABSTRACT
We have studied the association with the level of the endothelium dependent vasodilatation (EDVD) among 11 single nucleotide polymorphisms (SNPs) of 10 genes in 45 children suffering from diabetes mellitus type 1. Following polymorphisms have been studied: G894âT of the eNOS exon 7 and Т-786âС of the eNOS promotor, Ð1266âG of the Eln exon 16, Т-381âC of the NPPB promotor, Ð\D of the ACE, Arg60âHis of the LMP2, Met235âThr of the AGT, A1166âC of the ATR1, C-1562âT of the MMP9, C-1306âT of the MMP2, and С-8âG of the PSMA6. It was shown that children with genotypes G/T by eNOS (G894âT), G/G by Eln (Ð1266âG), C/C by NPPB (Т-381âC) and Ð/D by ACE genes have lower EDVD (Ð <0,05) than patients with others allelic variants of these genes, and this does not depend on duration of the disease, level of glicated hemoglobin and initial diameter of a humeral (brachial) artery. The combination of the above-stated genotypes influences most significantly on EDVD decrease (r=0,61; Ð <0,01), comparing to each genotype separately.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Dilatation, Pathologic/genetics , Nitric Oxide Synthase Type III/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Single Nucleotide , Receptors, Atrial Natriuretic Factor/genetics , Tropoelastin/genetics , Adolescent , Brachial Artery/metabolism , Brachial Artery/pathology , Child , Cysteine Endopeptidases/genetics , Cysteine Endopeptidases/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/pathology , Dilatation, Pathologic/complications , Dilatation, Pathologic/metabolism , Dilatation, Pathologic/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Female , Gene Expression , Genotype , Humans , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nitric Oxide Synthase Type III/metabolism , Peptidyl-Dipeptidase A/metabolism , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Receptors, Atrial Natriuretic Factor/metabolism , Tropoelastin/metabolismABSTRACT
To test the hypothesis that telomerase reverse transcriptase (TERT) as an RNA-dependent RNA polymerase could be involved in the amplification of microRNA (miRNA), we have determined the levels of immature and mature miRNA in cultured neonatal rat cardiomyocytes, during the silencing of TERT by siRNA. The silencing of the TERT gene led to the reduction of both telomerase activity and the TERT mRNA expression when compared with scrambled RNA. TERT gene silencing resulted in the decrement of three studied mature miRNAs levels: miRNA-21, miRNA-29a and miRNA-208a when compared with scrambled RNA; but miRNA-1, it was not changed significantly. At the same time, levels of immature miRNA-1 and miRNA-208a were not changed, although the levels of immature miRNA-29a and pri-miRNA-1 were decreased. The data obtained allow us to permit that TERT is a genome-independent source of mature miRNA, and the changes in telomerase activity can significantly influence the level of miRNA in cardiomyocytes.
Subject(s)
MicroRNAs/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Telomerase/metabolism , Animals , Cell Hypoxia , Cell Survival , Cells, Cultured , Gene Silencing , Myocardium/cytology , Myocytes, Cardiac/cytology , Rats, WistarABSTRACT
Study of 17 single nucleotide polymorphisms has been performed to determine the factors of genetic predisposition to essential hypertension. Polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length, allele specific PCR or real-time PCR was used for genotyping of 17 single nucleotide polymorphisms in 14 genes in 145 children with essential hypertension and 144 healthy persons with following complex multivariate statistical analysis. Two single nucleotide polymorphisms--MMP9 (C(-1562) --> T) and NOS3 (Glu298 --> Asp)--rs3918242 and rs1799983--were shown to represent the main independent effects with the highest predictive potential (77.1% as indicated by binary logistic regression and 74.6% testing accuracy shown by Multifactorial Dimensionality Reduction). MMP9 (C(-1562 --> T) and NOS3 (Glu298 --> Asp) potentially may be used to create predictive algorithm for determination of predisposition to arterial hypertension in children.
