engleski

Frequency of AGT, ACE, AGTR1, ADRB1, UMOD and ADIPOQ genetic polymorphisms in prehypertension

Arterial hypertension (AH) is a major independent risk factor for cardiovascular (CV) and cerebral mortality and morbidity and is one of the major risk factors for chronic kidney disease. Prehypertension (PHT) i.e. high normal arterial pressure (AP) is also associated with CV risk and risk of progression in AH. Previous studies of the genetic background of PHT have been insufficiently conducted, and the results indicate a possible association of certain genes involved in the etiopathogenesis of AH and PHT. The lack and sometimes inconsistency of information and results on the role of gene polymorphisms in the etiopathogenesis of PHT were the impetus to this research. Our hypothesis was that polymorphisms rs2004776 AGT, rs1799752 ACE, rs5196 AGTR1, rs1801253 ADRB1, rs13333226 UMOD and rs266729 and rs17300539 ADIPOQ, which are associated with AH and metabolic syndrome, are more common in individuals with high normal AP i.e. prehypertension than in individuals with optimal and normal AP. We chose these polymorphisms because these genes are involved in various mechanisms that lead to an increase in AP and metabolic complications. In this cross-sectional, observational study, 601 subjects were included ; 319 with high normal AP (PHT, 120/80–139/89 mmHg), both sexes, aged 20–45 years, and 282 subjects with normal and optimal AP as a control group (NT). The results showed that the investigated gene polymorphisms are not found more frequently in the PHT group than in the NT. However, a significantly lower frequency of the heterozygous genotype rs266729 ADIPOQ was found in PHT (35.1%), compared to the frequency in NT (44.7%), P = 0.03. The incidence of PHT is 0.66-fold lower in heterozygous (C/G) carriers of rs266729 ADIPOQ. We demonstrated a significant association of the minor allele G rs13333228 UMOD with lower values of systolic and diastolic AP and the minor allele A rs17300539 ADIPOQ with lower values of systolic AP. Additionally, our study resulted in the identification of two haplotypes that were significantly positively associated with PHT formation. The first is hIAGC with a 41% higher probability of developing PHT (rs1799752 ACE + rs13333226 UMOD + rs17300539 ADIPOQ + rs266729 ADIPOQ). The frequency of this haplotype is 8% higher in PHT than in NT. The second haplotype is hIAGCA and is 47% more likely to develop PHT (rs1799752 ACE + rs13333226 UMOD + rs17300539 ADIPOQ + rs266729 ADIPOQ + rs5186 AGTR1). The frequency of hIAGCA in NT is 18%, while in PHT it is 23%. Furthermore, the finding of a model of multivariate prediction of PHT (gene-gene-other determined parameters interaction) which includes a pro-prehypertensive significant effect of male sex, body weight, heart rate, fasting glucose concentration and total cholesterol is significant, while the protective effect within this model have body height and heterozygous (G/A) genotype rs17300539 ADIPOQ. We pointed to the possible importance of genes encoding proteins involved in essential biological pathways responsible for AP control, which include, among others, the renin-angiotensin-aldosterone system, the kidney, the central nervous system, blood vessels, and adipose tissue. In conclusion, the performed analyzes confirmed and showed the presence of significant gene - gene and gene - other determined parameters interactions (anthropometric, biochemical, environmental factors), but also gene - gene - other determined parameters in the etiology of PHT.

gene polymorphisms ; etiology ; observational study ; prehypertension ; risk factors

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