Association of Angiotensinogen Gene Polymorphism with Erythropoietin-Induced Hypertension: A Preliminary Report.

Abstract

The association of the angiotensinogen (AGT) gene variation at codon 235, the T235 variant, with hypertension induced by erythropoietin (Epo) was investigated 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/dl and a hematocrit (Ht) of less than 30%. During the run-in period, blood pressure was well controlled with an appropriate salt restricted diet and/or antihypertensive treatment. The patients were then given 6,000 IU of Epo once a week until 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, hypertension (defined as an increase in mean blood pressure greater than 10 mmHg) was found in 11 cases (22%), all of who carried the homozygous T allele (T/T). On the other hand, the frequency of T/T in patients who did not develop 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 with Epo-induced hypertension were the T allele, gender (male), and the degree of increase in Ht, in descending order. Our preliminary research indicates that individuals who carry two copies of the T allele, i.e., who are homozygous for T, are highly susceptible to development of hypertension when subjected to Epo. These results suggest that the AGT T235 variant may be the primary gene responsible for the development of Epo-induced hypertension.

Prevention of Erythropoietin-Associated Hypertension

“…[37][38][39][40][41][42][43][44][45][46][47] Nevertheless, Epo has potentially beneficial effects on the endothelial and neuroprotection, maybe via antiapoptosis. 48 -51 In our previous study, we demonstrated that the Epo receptor exists in various progenitor cell surfaces and tissues.…”

2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease

“…It has also been reported that patients with a family history and past history of hypertension tend to have hypertension because of the presence of risk for the disease [180]. A relationship between the inherited factors for hypertension and the T allele of M235T angiotensinogen gene polymorphism has also been reported [181].…”

Effect of erythropoietin on the expression of dynamin-related protein-1 in rat renal interstitial fibrosis

“…A previous study found that EPO can ameliorate anemia, inhibit inflammatory reactions, promote the growth of blood vessels, inhibit apoptosis, and reduce the expression of cytokines and inflammatory factors, thereby protecting organs from damage (30). In recent years, a large number of animal experiments have shown that EPO can delay the progress of chronic kidney disease and improve the degree of interstitial fibrosis, and has a certain renal protective effect (31)(32)(33). A study conducted by Nakazawa et al demonstrated that EPO is able to inhibit renal tubule cell apoptosis, thereby reducing the degree of renal interstitial fibrosis (34).…”