Original Contribution
The American Journal of Gastroenterology (2005) 100, 636–642; doi:10.1111/j.1572-0241.2005.41168.x
A1166C Angiotensin II Type 1 Receptor Gene Polymorphism May Predict Hemodynamic Response to Losartan in Patients with Cirrhosis and Portal Hypertension
Silvia Sookoian MD1, Gustavo Castaño MD1, Silvia I García PhD1, Pedro Viudez MD1, Claudio González MD1 and Carlos J Pirola PhD1
1Cardiología Molecular, Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Buenos Aires; Departamento de Medicina interna, Hospital José M. Penna; and Sección Gastroenterología, Hospital Naval, Argentina
Correspondence: Carlos Pirola, PhD, Instituto de Investigaciones Médicas, A Lanari, Cardiología Molecular, Combatientes de Malvinas 3150, Buenos Aires, Argentina (1427)
Received 14 July 2004; Revised 0000; Accepted 8 September 2004.
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.
