Early inflammatory and metabolic changes in association with AGTR1 polymorphisms in prehypertensive subjects.
BACKGROUND
The Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in 2003 created a prehypertension category for persons with blood pressures ranging from systolic blood pressure (SBP) of 120-139 mm Hg or diastolic blood pressure (DBP) from 80 to 89 mm Hg, due to increased risk of cardiovascular disease.


METHODS
Our study utilized the University of California-San Diego (UCSD) Twin Hypertension Cohort. We measured comprehensive plasma cholesterol levels and metabolic (glucose, insulin, leptin) and inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP), free fatty acids) to determine the differences between normotensive and prehypertensive subjects. Additionally, we determined whether angiotensin II receptor type-1 (AGTR1) polymorphisms, previously associated with hypertension, could predict prehypertension.


RESULTS
A total of 455 white subjects were included in the study (mean age 37.1 years). Prehypertensive subjects were older with greater body mass index (BMI) than the normotensives, and after adjusting for sex and age, had greater plasma glucose, insulin, and IL-6. The common AGTR1 A1166C (rs5186) polymorphism in the 3'-UTR region, particularly the presence of the 1166C allele, which fails to downregulate gene expression, predicted greater likelihood of being in the prehypertension group and higher SBP. A lesser-studied polymorphism in intron-2 of AGTR1 (A/G; rs2276736) was associated with plasma high-density lipoprotein (HDL) and apolipoprotein A-1. In a subgroup analysis of nonobese subjects (N = 405), similar associations were noted.


CONCLUSIONS
Prehypertensive subjects already exhibit early pathophysiologic changes putting them at risk of future cardiovascular disease, and AGTR1 may also contribute to this increased risk. Further investigation is needed to confirm these findings and the precise molecular mechanisms of action.
Fung
Maple M
MM
Veterans Affairs San Diego Healthcare System, La Jolla, California, USA. mafung@ucsd.edu
Rao
Fangwen
F
Poddar
Sameer
S
Mahata
Manjula
M
Khandrika
Srikrishna
S
Mahata
Sushil K
SK
O'Connor
Daniel T
DT
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000235:genetics*; D002097:C-Reactive Protein / Q000032:analysis; D002140:California; D002784:Cholesterol / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016018:Least-Squares Analysis; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D058246:Prehypertension / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
C544065:AGTR1 protein, human; D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; C508600:IL6 protein, human; D018836:Inflammation Mediators; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D044140:Receptor, Angiotensin, Type 1; D002097:C-Reactive Protein; D002784:Cholesterol