Interplay between miR-155, AT1R A1166C polymorphism, and AT1R expression in young untreated hypertensives.
BACKGROUND
A silent polymorphism (+1166 A/C single-nucleotide polymorphism) localized in the 3'-UTR (untranslated region) of the human angiotensin II type-1 receptor (AT1R) has been associated with hypertension and cardiovascular complications. The +1166 A/C is recognized by a specific microRNA-155 (miR-155), which is base-pairing complementary with the +1166 A-allele but not with the mutant +1166 C allele. Aim of our study was to investigate the interplay between miR-155 and AT1R protein expression.


METHODS
Sixty-four subjects were selected for the +1166 A/C from the cohort of hypertensives (n = 573) of the Hypertension and Ambulatory Recording Venetia Study (HARVEST): 25 were homozygous for the 1166 A allele, 20 heterozygous, and 19 homozygous for the 1166 C allele.


RESULTS
miR-155 expression was significantly decreased in subjects with CC genotype in comparison to AA and AC genotype. AT1R protein expression was significantly increased in the CC group in comparison to AA and AC (P < 0.01) although AT1R mRNA expression was not significantly different in the three groups. AT1R protein expression was positively correlated with systolic and diastolic blood pressure and negatively correlated with miR-155 expression level. Plasma transforming growth factor-β1 (TGF-β1) may have a modulator role in the interplay between miR-155 and AT1R protein expression as it was correlated negatively with miR-155 expression and positively with AT1R protein expression in subjects with CC genotype.


CONCLUSIONS
The interplay between miR-155 expression, +1166C polymorphism, and AT1R protein expression may have a role in the regulation of blood pressure.
Department of Clinical and Experimental Medicine, University of Padova Medical School, Italy.
Giulio
G
Ceolotto
Italia
I
Papparella
Alessia
A
Bortoluzzi
Giacomo
G
Strapazzon
Fabio
F
Ragazzo
Paolo
P
Bratti
Aline S C
AS
Fabricio
Elisa
E
Squarcina
Massimo
M
Gion
Paolo
P
Palatini
Andrea
A
Semplicini
D020413:3' Untranslated Regions; D000328:Adult; D017668:Age of Onset; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D007558:Italy / Q000453:epidemiology; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000097:blood
D020413:3' Untranslated Regions; C544065:AGTR1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1