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
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.
Subject(s)
Genetic Predisposition to Disease , Hemodynamics/genetics , Hypertension/genetics , Polymorphism, Single Nucleotide , Adolescent , Algorithms , Case-Control Studies , Child , Data Interpretation, Statistical , Essential Hypertension , Humans , Logistic Models , Multivariate Analysis , Odds Ratio , Predictive Value of TestsABSTRACT
Proteasomal activity in isolated monocytes from subjects with different variants of large multifunctional proteases genes -LMP2 (Arg60-->His allelic polymorphism) and LMP7 (Lys145-->Gln allelic polymorphism) was determined. Trypsin-like activity of proteasome was 1.6-times (P = 0.19) higher at Arg/Arg genotype comparing to His/His genotype, and 2-fold lower than at Arg/His genotype. The highest chymotrypsin-like activity of proteasome was observed in heterozygotes (on 29.7% higher comparing to Arg/Arg genotype, P = 0.43) and lowest in homozygotes His/His (on 29.7% less comparing to Arg/Arg genotype, P = 0.40). Level of RNA expression in isolated monocytes detetermined by use of RT-PCR did not differed significantly in subjects with different genotypes. Data obtained indicate that LMP2 allelic polymorphism impact peptidase activity of immunoproteasome.
