Lipid Disorders and Essential Arterial Hypertension Risk Depending on Agtr1 (Rs5186) and VDR (Rs2228570) Genes Polymorphism

Abstract

Objective:Hypertension and dyslipidemia represent two of the most relevant modifiable cardiovascular risk factors and they often coexist. The aim of the research was to study lipid disorders and essential arterial hypertension (EAH) risk depending on AGTR1 (rs5186) and VDR (rs2228570) genes polymorphism.Design and method:100 subjects with EAH and target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Among them, 70,83% females and 29,17% males, mean age 57,86 ± 7,81y.o. Control group consisted of 60 practically healthy individuals of relevant age. The lipid panel parameters, such as: TC (Total cholesterol), TG (Triglycerides), LDL-C (Low-density lipoprotein cholesterol), HDL-C (High-density lipoprotein cholesterol) were investigated in blood plasma, using diagnostic kits “Accent 200” (Poland). The atherogenic index (IA) was calculated by the formula: (TC – HDL-C)/ HDL-C. Gene polymorphism of AGTR1 (rs5186) and VDR (rs2228570), was detected by polymerase chain reaction (PCR).Results:Decreased HDL-C is associated with 2nd and 3d degrees of EAH (p = 0,048). The risk of EAH increases in C-allele carriers of AGTR1 (rs5186) gene with hypercholesterolemia (TC> 5,0mmol/l) 1,5 times (OR–2,50;p = 0,048), with an increase in LDL-C and IA – 1,58 and 2,12 times (OR–10,80;p = 0,019), respectively. Homozygous carriers of the minor A-allele had extremely higher concentrations of TC, atherogenic LDL-C and IA, than GG-carriers – by 9,29%, 11,11% and 12,80% (pAA<0,05), respectively. Risk of EAH increases with hypertriglycerolemia 1,89 times (OR–2,93;p = 0,03) and with the increase in LDL-C – 1,26 times (OR–3,60;p = 0,038) in AA-genotype carriers of VDR (rs2228570) gene. Risk of EAH synergistically escalates almost twice in A-allele carriers of VDR (rs2228570) gene with a decrease of HDL-C (OR–2,88;p = 0,046) and the increase of IA (OR–2,70;p = 0,039), significantly only in AG-carriers though. ANOVA analysis confirmed the association of VDR (rs2228570) gene with the increase in IA (F = 3,80;p = 0,05).Conclusions: The EAH risk escalates with hypercholesterolemia, elevated both LDL-C and IA in C-allele carriers of AGTR1 (rs5186) gene, as well as with decreased HDL-C and increased IA in A-allele carriers VDR (rs2228570) in the observed.

Endothelium function biomarkers and carotid intima-media thickness changes in relation to NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphism in the essential arterial hypertension

“…Exclusion criteria have been described previously (Dzhuryak et al 2020;Repchuk et al 2021;Semianiv et al 2021;Sydorchuk et al 2020a, b). The patients with EAH stage 3 (established CV disease, chronic kidney diseases, CKD) -with estimated glomerular filtration rate (eGFR) decline <30 ml/min/1.73 m 2 ), secondary arterial hypertension, EAH patients with complications of HMOD, chronic heart failure (CHF) higher than II functional class (NYHA III-IV), diabetes mellitus type I (T1DM), sub-and de-compensated diabetes mellitus type 2 (T2DM) (with diabetic target-organ damage), malignant or uncontrolled arterial hypertension, sub-and de-compensated liver diseases (triple growth over the normal level of aspartate aminotransferase, alanine aminotransferase), bronchial asthma, chronic obstructive pulmonary disease of III-IV stage with C or D risk value (GOLD 2019), exacerbated infectious diseases or during unstable remission, psychological disorders, oncologic problem of any location, administration of oral corticosteroids or contraceptives, and pregnancy or lactation were excluded.…”

“…DNA fragments of analyzed genes amplified by Quantitative Real-Time PCR (qRT-PCR) with specific for each gene TaqMan probes and genotyping with TaqMan Genotyping Master Mix on CFX96 Touch™ RT-PCR Detection System (Bio-Rad Laboratories, Inc., USA). The genotyping protocol was described in our previous publications (Dzhuryak et al 2020;Sydorchuk et al 2020 a, b;Kamyshna et al 2021;Repchuk et al 2021;Semianiv et al 2021). Alleles' discrimination of NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms was analyzed by licensed CFX96 RT-PCR Detection System Software (Microsoft, USA).…”

“…Under these conditions, the excessive production of the endothelial vasoconstriction factors is associated with a parallel decrease of NO availability, reduced endothelial NO production, and depressed endothelial nitric oxide synthase (eNOS) expression (Carrizzo et al 2020). Therefore, there is an assumption that the rate of these processes can be, at least partially, determined by genes that regulates RAAS activity or code the enzymes expression or synthesis associated with hypertrophy and remodeling of the vascular smooth muscles (Sydorchuk et al 2013(Sydorchuk et al , 2015(Sydorchuk et al , 2020aJi et al 2017;Charoen et al 2019;Smyth et al 2019;Dzhuryak et al 2020;Tegegne et al 2020;Repchuk et al 2021;Semianiv et al 2021). The relationship between ED markers, vessels wall thickness, and genetic predisposition in hypertensive patients has not been fully revealed yet.…”

The role of NOS3 (rs2070744) and GNB3 (rs5443) genes’ polymorphisms in endothelial dysfunction pathway and carotid intima-media thickness in hypertensive patients

“…DNA fragments of analyzed genes amplified by qRT-PCR with specific for each gene TaqMan probes and genotyping with TaqMan Genotyping Master Mix on CFX96 Touch™ RT-PCR Detection System (Bio-Rad Laboratories, Inc., USA). The genotyping protocol was described in our previous publications (Dzhuryak et al 2020;Sydorchuk et al 2020aSydorchuk et al , 2020bRepchuk et al 2021;Semianiv et al 2021). Alleles' discrimination of NOS3 (rs2070744) and GNB3 (rs5443) gene polymorphisms was analyzed by licensed CFX96 RT-PCR Detection System Software (Microsoft, USA).…”

“…Soluble vascular cell adhesion molecule-1 (sVCAM-1) promotes inflammatory cells adhesion to the vascular endothelium and facilitates its migration through the endothelium membrane (Dörr et al 2012;Tchalla et al 2015Tchalla et al , 2018. Some evidence prove that these processes might be at least partially genetically determined by genes regulating RAAS or NO activity or code the enzymes' expression or synthesis, or associate with hypertrophy and remodeling of vascular smooth muscles (Sydorchuk et al 2013(Sydorchuk et al , 2015(Sydorchuk et al , 2020aJi et al 2017;Pimphen Charoen et al 2019;Smyth et al 2019;Dzhuryak et al 2020;Tegegne et al 2020;Repchuk et al 2021;Semianiv et al 2021). However, the mechanisms that orchestrate the balance between NO and EDCF, genetic predisposition to endothelial dysfunction in hypertensive patients still remain to be determined.…”