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Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents.

ABSTRACT: Epidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood.This cross-sectional study enrolled 709 participants aged 12-15 years. The subjects were genotyped for AGT (M235 T, rs699), AGTR1 (A1166C, rs5186), and ACE (rs4340) gene polymorphisms using real-time and conventional polymerase chain reactions. Blood pressure and anthropometric parameters were measured.The prevalence of HBP was 38.6% and was more frequently detected in boys than in girls (47.9% vs. 29.5%; p < 0.001). No significant differences in the frequencies of the AGT or AGTR1 genotypes or alleles between boys and girls were observed, except for ACE genotypes. The mean SBP value was higher in HBP subjects with ACE ID genotype compared to those with ACE II homozygotes (p = 0.04). No significant differences in BP between different AGT and AGTR1 genotype groups were found. Boys who carried the ACE ID + DD genotypes had higher odds of having HBP than carriers of the ACE II genotype did (controlling for the body mass index (BMI): ORMH = 1.83; 95% CI, 1.11-3.02, p = 0.024; and controlling for waist circumference (WC): ORMH = 1.76; 95% CI, 1.07-2.92, p = 0.035). These associations were not significant among girls. The same trend was observed in the multivariate analysis - after adjustment for BMI and WC, only boys with ACE ID genotype and ACE ID + DD genotypes had statistically significantly increased odds of HBP (aOR = 2.05; 95% CI, 1.19-3.53 (p = 0.01) and aOR = 1.82; 95% CI, 1.09-3.04 (p = 0.022), respectively).The evaluated polymorphisms of the AGT and AGTR1 genes did not contribute to the presence of HBP in the present study and may be seen as predisposing factors, while ACE ID genotypes were associated with significantly increased odds for the development of HBP in the Lithuanian child and adolescent population - especially in boys.

SUBMITTER: Simonyte S

PROVIDER: S-EPMC5598068 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents.

Simonyte Sandrita S Kuciene Renata R Medzioniene Jurate J Dulskiene Virginija V Lesauskaite Vaiva V

BMC medical genetics 20170913 1

<h4>Background</h4>Epidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood.<h4>Methods</h4>This cross-sectional study enrolled 709 participants aged 1 ...[more]

PMID: 28903744

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Project description:OBJECTIVES:Recently, genome-wide associated studies have identified several genetic loci that are associated with elevated blood pressure and could play a critical role in intracellular calcium homeostasis. The aim of this study was to assess the associations of ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms with high blood pressure (HBP) among Lithuanian children and adolescents aged 12-15 years. STUDY DESIGN AND PARTICIPANTS:This was a cross-sectional study of a randomly selected sample of 646 12-15-year-old adolescents who participated in the survey 'The Prevalence and Risk Factors of HBP in 12-15?Year-Old Lithuanian Children and Adolescents (from November 2010 to April 2012)'. Anthropometric parameters and BP were measured. The participants with HBP were screened on two separate occasions. Subjects were genotyped ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms using real-time PCR method. RESULTS:The prevalence of HBP was 36.7%, significantly higher for boys than for girls. In the multivariate analysis, after adjustment for body mass index and waist circumference, boys with CACNB2 CG genotype, CACNB2 GG genotype and CACNB2 CG +GG?genotype had higher odds of having HBP in codominant (adjusted OR (aOR)=1.92; 95%?CI 1.16 to 3.18, p=0.011; and aOR=2.64; 95%?CI 1.19 to 5.90, p=0.018) and in dominant (aOR=2.05; 95%?CI 1.27 to 3.30, p=0.003) inheritance models. Girls carrying CACNB2 CG genotype and CACNB2 CG +GG?genotype had increased odds of HBP in codominant (aOR=1.82; 95%?CI 1.02 to 3.24, p=0.044) and in dominant (aOR=1.89; 95%?CI 1.09 to 3.28, p=0.023) inheritance models. Furthermore, significant associations were found in additive models separately for boys (aOR=1.72; 95%?CI 1.20 to 2.46, p=0.003) and girls (aOR=1.52; 95%?CI 1.05 to 2.20, p=0.027). No significant association was found between ATP2B1 gene polymorphism and the odds of HBP. CONCLUSIONS:Our results indicate that CACNB2 gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 years.

Project description:Emerging evidence has demonstrated that (pro)renin receptor (PRR)-mediated activation of intrarenal renin-angiotensin system (RAS) plays an essential role in renal handling of Na+ and water balance and blood pressure. The present study tested the possibility that the intrarenal RAS served as a molecular target for the protective action of ELABELA (ELA), a novel endogenous ligand of apelin receptor, in the distal nephron. By RNAscope and immunofluorescence, mRNA and protein expression of endogenous ELA was consistently localized to the collecting duct (CD). Apelin was also found in the medullary CDs as assessed by immunofluorescence. In cultured CD-derived M1 cells, exogenous ELA induced parallel decreases of full-length PRR (fPRR), soluble PRR (sPRR), and prorenin/renin protein expression as assessed by immunoblotting and medium sPRR and prorenin/renin levels by ELISA, all of which were reversed by 8-bromoadenosine 3',5'-cyclic monophosphate. Conversely, deletion of PRR in the CD or nephron in mice elevated Apela and Apln mRNA levels as well as urinary ELA and apelin excretion, supporting the antagonistic relationship between the two systems. Administration of exogenous ELA-32 infusion (1.5 mg·kg-1·day-1, minipump) to high salt (HS)-loaded Dahl salt-sensitive (SS) rats significantly lowered mean arterial pressure, systolic blood pressure, diastolic blood pressure, and albuminuria, accompanied with a reduction of urinary sPRR, angiotensin II, and prorenin/renin excretion. HS upregulated renal medullary protein expression of fPRR, sPRR, prorenin, and renin in Dahl SS rats, all of which were significantly blunted by exogenous ELA-32 infusion. Additionally, HS-induced upregulation of inflammatory cytokines (IL-1β, IL-2, IL-6, IL-17A, IFN-γ, VCAM-1, ICAM-1, and MCP-1), fibrosis markers (TGF-β1, FN, Col1A1, PAI-1, and TIMP-1), and kidney injury markers (NGAL, Kim-1, albuminuria, and urinary NGAL excretion) were markedly blocked by exogenous ELA infusion. Together, these results support the antagonistic interaction between ELA and intrarenal RAS in the distal nephron that appears to exert a major impact on blood pressure regulation.

Dataset Information

Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents.

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Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents.

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