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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hajjar
Ihab
I
Harvard Medical School, Institute for Aging Research/Hebrew SeniorLife/Beth Israel Deaconess Medical Center, Division of Gerontology, Boston, MA 02130, USA. ihabhajjar@hrca.harvard.edu
Sorond
Farzaneh
F
Hsu
Yi-Hsiang
YH
Galica
Andrew
A
Cupples
L Adrienne
LA
Lipsitz
Lewis A
LA
D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000235:genetics*; D016852:Housing for the Elderly; D006801:Humans; D009483:Neuropsychological Tests; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics; D012039:Regional Blood Flow; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000235:genetics*; D017585:Ultrasonography, Doppler, Transcranial
D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A