Interactions between gender and the angiotensin type 1 receptor gene polymorphism

Area of Science:

• Cardiovascular Physiology
• Human Genetics
• Renal Physiology

Background:

• Cardiovascular effects of angiotensin II are mediated by the angiotensin II type 1 receptor (AGT1R).
• The AGT1R gene A1166-->C polymorphism is linked to hypertension.
• Interactions between gender, blood pressure, and AGT1R gene polymorphisms are not well understood.

Purpose of the Study:

• To investigate the interplay between gender, AGT1R A1166-->C genotype, and blood pressure regulation.
• To examine how gender and AGT1R genotype influence the renal hemodynamic response to angiotensin II.

Main Methods:

• Studied 81 healthy normotensive individuals categorized by gender and AGT1R genotype (AA vs. AC/CC).
• Measured serial blood pressures and performed graded angiotensin II infusions in a subset of 52 participants.
• Assessed renal hemodynamic function using inulin and para-aminohippurate clearance techniques.

Main Results:

• Men with the AC/CC genotype had higher blood pressure than AA genotype men; this was not observed in women.
• A significant interaction between gender and AGT1R genotype affected blood pressure determination.
• Glomerular filtration rate (GFR) decline post-angiotensin II infusion was best predicted by gender and genotype, with a trend for AA females to show a greater GFR reduction.

Conclusions:

• Significant interactions exist between gender, the AGT1R A1166-->C gene polymorphism, and blood pressure in young healthy individuals.
• Renal hemodynamic response to angiotensin II is influenced by both gender and AGT1R genotype.