A1166C angiotensin II type 1 receptor gene polymorphism may predict hemodynamic response to losartan in patients with cirrhosis and portal hypertension.

Abstract

OBJECTIVE:

Losartan, a dose of 25 mg/day, has been found to be effective in 50% of patients with portal hypertension without adverse effects. We evaluated the relationship between genetic polymorphisms of the renin-angiotensin system (A1166C angiotensin II type 1 receptor (AT1R), angiotensinogen T174M and M235T, and angiotensin-converting enzyme I/D) and the effects of losartan on portal and systemic hemodynamic in patients with cirrhosis and portal hypertension.

METHODS:

We performed a longitudinal study that included 23 consecutive patients with cirrhosis and esophageal varices who received 25 mg/day of losartan during 12 wk. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured at baseline and after treatment. Genomic DNA was extracted from peripheral blood leukocytes; genetic polymorphisms of the renin-angiotensin system were investigated by polymerase chain reaction and restriction fragment length polymorphisms.

RESULTS:

The homozygous patients for AT1R A allele showed higher pulmonary-wedged and free hepatic venous pressure on baseline. After treatment, they showed a higher decrease of HVPG (32.5%+/- 19.2) in comparison with patients with AC/CC genotype (2.4%+/-18.9), p < 0.01. Ten of 15 patients with AA genotype were responders, while only one of eight with AC/CC genotype (p < 0.002); genotype AA showed a positive predictive value of 66.6% and negative predictive value of 87.5%.

CONCLUSIONS:

These results suggest that there is a relationship between the AT1R A1166C polymorphisms and the therapeutic response to losartan. The genetic testing may be used as a predictive factor of this response.

• Authors: Silvia Sookoian, Gustavo Castaño, Silvia I García, Pedro Viudez, Claudio González, Carlos J Pirola
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 100 Issue 3 Pg. 636-42 (Mar 2005) ISSN: 0002-9270 [Print] United States
• PMID: 15743363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Receptor, Angiotensin, Type 1
• Losartan

Topics

• Adolescent
• Adult
• Aged
• Angiotensin II Type 1 Receptor Blockers (pharmacology, therapeutic use)
• Blood Pressure (drug effects, genetics)
• Chromatography, High Pressure Liquid
• Esophageal and Gastric Varices (physiopathology)
• Female
• Hemodynamics (drug effects)
• Humans
• Hypertension, Portal (physiopathology)
• Liver Circulation (drug effects)
• Liver Cirrhosis (drug therapy, physiopathology)
• Longitudinal Studies
• Losartan (pharmacology, therapeutic use)
• Male
• Middle Aged
• Polymorphism, Genetic
• Receptor, Angiotensin, Type 1 (genetics)