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Renin angiotensin system gene polymorphisms and cerebral blood flow regulation: the MOBILIZE Boston study.

ABSTRACT: Our objective was to investigate the associations between polymorphisms in representative genes of the renin angiotensin system with measures of cerebral blood flow regulation in older adults.Participants in this analysis were white subjects (n=335) in the MOBILIZE Boston study (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston), an observational study of community-dwelling elders who underwent transcranial Doppler while sitting and standing and during hypercapnea and hypocapnea. Autoregulation phenotype was the change in cerebrovascular resistance from sit to stand. Vasoreactivity phenotype was the slope of the change in cerebrovascular conductance versus change in end-tidal CO2. A total of 33 tagged single nucleotide polymorphisms were selected in the angiotensinogen gene, the angiotensin converting enzyme gene, and the angiotensin receptor gene. Regression analyses adjusted for age, gender, body mass index, mean arterial blood pressure, stroke, and use of antihypertensives were conducted for each single nucleotide polymorphism and outcome. Bonferroni corrections were used to adjust P values for multiple testing.In the angiotensinogen gene, only the rs699 single nucleotide polymorphism was associated with vasoreactivity after Bonferroni correction (P=0.00028). Homozygous carriers of the CC genotype of this single nucleotide polymorphism had lower vasoreactivity compared with the CT or TT genotypes. There were no significant associations with autoregulation measures. None of the single nucleotide polymorphisms in the other genes were associated with our phenotypes.This analysis suggests that the angiotensinogen gene may be involved in vasoreactivity independent of blood pressure. Larger studies are needed to confirm the role of this gene in cerebrovascular health and aging.

SUBMITTER: Hajjar I

PROVIDER: S-EPMC3563282 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Renin angiotensin system gene polymorphisms and cerebral blood flow regulation: the MOBILIZE Boston study.

Hajjar Ihab I Sorond Farzaneh F Hsu Yi-Hsiang YH Galica Andrew A Cupples L Adrienne LA Lipsitz Lewis A LA

Stroke 20100225 4

<h4>Background and purpose</h4>Our objective was to investigate the associations between polymorphisms in representative genes of the renin angiotensin system with measures of cerebral blood flow regulation in older adults.<h4>Methods</h4>Participants in this analysis were white subjects (n=335) in the MOBILIZE Boston study (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston), an observational study of community-dwelling elders who underwent transcranial Dop ...[more]

PMID: 20185782

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Project description: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.

Dataset Information

Renin angiotensin system gene polymorphisms and cerebral blood flow regulation: the MOBILIZE Boston study.

Publications

Renin angiotensin system gene polymorphisms and cerebral blood flow regulation: the MOBILIZE Boston study.

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