Association of angiotensinogen gene polymorphism with erythropoietin-induced hypertension: a preliminary report

The association of the angiotensinogen (AGT) gene variation at codon 235, t he T235 variant, with hypertension induced by erythropoietin (Epo) was inve stigated in patients with progressive renal disease requiring treatment for renal anemia with Epo. The subjects for the study were patients with renal diseases with serum creatinine concentration exceeding 2 mg/dI and a hemat ocrit (Ht) of less than 30%. During the run-in period, blood pressure was w ell controlled with an appropriate salt restricted diet and/or antihyperten sive treatment. The patients were then given 6,000 IU of Epo once a week un til the Ht rose by 5%. For the overall patient group, AGT gene polymorphism analysis revealed T235T (T/T) in 31 cases (61%), M235T (M/T) in 19 cases ( 37%), and M235M (M/M) in 1 case (2%). In response to treatment with Epo, hy pertension (defined as an increase in mean blood pressure greater than 10 m mHg) was found in 11 cases (22%), all of who carried the homozygous T allel e (T/T). On the other hand, the frequency of T/T in patients who did not de velop hypertension was 50% (T/T:T/M=20:19 cases), indicating a significant difference (p=0.003 by Chi-square). Variables estimated to be associated wi th Epo-induced hypertension were the T allele, gender (male), and the degre e of increase in Ht, in descending order. Our preliminary research indicate s that individuals who carry two copies of the T allele, Le., who are homoz ygous for T, are highly susceptible to development of hypertension when sub jected to Epo. These results suggest that the AGT T235 variant may be the p rimary gene responsible for the development of Epo-induced hypertension.