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

Abstract

Objective. The aim of the present study was to clarify the endothelial function biomarkers and carotid “intima media” thickness (IMT) changes in relation to GNB3 (rs5443) and NOS3 (rs2070744) genes polymorphism in the essential arterial hypertension (EAH). Methods. One-hundred EAH patients (48 – control) participated in the case-control study. Soluble vascular cell adhesion molecule (sVCAM-1), total NO metabolites (NO2 –+NO3 –), transcriptional activity of NOS3 gene, endothelium-dependent flow-mediated dilation of the brachial artery (FMD BA), and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping was performed by TaqMan probes (CFX96™Real-Time PCR). Results. The connection of NOS3 (rs2070744) with decreased total NO metabolites (F=71.11; p<0.001), reduced NOS3 genes transcription activity (F=8.71; p<0.001) and increased sVCAM-1 (F=6.96; p=0.002), especially in the C-allele carriers (particularly in CC-genotype patients with lower NO – 16.46% and 40.88%; p<0.001), lowered the transcription activity of NOS3 gene – 46.03% 7 times (p<0.001), and become higher sVCAM-1 – 35.48% and 89.48% (p<0.001), respectively. ANOVA did not confirm the association of GNB3 (rs5443) gene with endothelial function and carotid IMT. Severe EAH was associated with increased carotid IMT – 50.0% (p<0.001) and 57.14% (p=0.007), wider carotid arteries – 17.36% (p=0.012) and 21.79% (p=0.004), and decreased NOS3 genes transcription activity – 34.54% (p=0.003). Atherosclerotic plaques were unilateral – 24.77% (χ2=5.35; p=0.021) or bilateral – 27.62% (χ2=5.79; p=0.016). IMT---gt---0.9 mm was followed by a higher BP (p<0.001), FMD BA 11.80% decrease with compensatory increase in carotid arteries diameters – 17.38% and 21.99% (p<0.001) and sVCAM-1 by 20.49% (p=0.005). Conclusion. NOS3 (rs2070744), but not GNB3 (rs5443), gene associated with the essential arterial hypertension severity relying upon the endothelial function impairment and NOS3 genes reduced transcription activity.

Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão

“… 6 , 15 No presente estudo, a análise da frequência alélica e genotípica não mostrou associação com hipertensão arterial, diferindo dos estudos que relataram essa associação em populações caucasianas, leste-asiáticas, alemãs e australianas. 5 , 7 , 15 Por outro lado, estudo realizado em outra população brasileira também não relatou associação entre os genótipos do polimorfismo C825T do gene GNB3 e a hipertensão arterial. 16 Isso pode ser devido à frequência desigual do alelo T entre diferentes etnias, 7 especialmente na população brasileira que é altamente mista.…”

“…Hypertension results from the interaction of genetic and environmental factors. 1 , 5 Considering that some genetic variants have the potential to contribute to susceptibility to certain diseases, 13 the present study examined the influence of the variant GNB3 rs5443:C>T in hypertensive and normotensive individuals.…”

“… 3 , 4 Foi relatado que a variante GNB3 rs5443:C>T, localizada no cromossomo 12p13, na região do éxon 10, está associada com a hipertensão arterial. 3 , 5 …”

“… 3 , 4 The variant GNB3 rs5443:C>T, located on chromosome 12p13, in the exon 10 region, has been reported to be associated with AH. 3 , 5 …”

“…Some studies have investigated the association between the variant GNB3 rs5443:C>T and blood pressure in other populations, and the results are controversial. 5 - 8 However, Chen et al 4 discussed how variant GNB3 rs5443:C>T can serve as early genetic marker of blood pressure salt sensitivity. The presence of the polymorphism generates a functional protein that triggers lipolysis through catecholamines, changing the lipid profile in the bloodstream.…”