The +1166C polymorphism in the AT1R gene is associated with decreased miR-155 expression and increased AT1R protein expression, which correlates with higher blood pressure 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. CONCLUSION: The interplay between miR-155 expression, +1166C polymorphism, and AT1R protein expression may have a role in the regulation of blood pressure.
Ceolotto et al. (Thu,) studied this question.