Kuriyama S, Tomonari H, Tokudome G, Kaguchi Y, Hayashi H, Kobayashi H, Horiguchi M, Ishikawa M, Hara Y, Hosoya T
Division of Nephrology, Saiseikai Central Hospital, Jikei University, Tokyo, Japan.
Hypertens Res. 2001 Sep;24(5):501-5. doi: 10.1291/hypres.24.501.
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.
在需要用促红细胞生成素（Epo）治疗肾性贫血的进行性肾病患者中，研究了血管紧张素原（AGT）基因第235密码子的变异体T235与Epo诱导的高血压之间的关联。研究对象为血清肌酐浓度超过2mg/dl且血细胞比容（Ht）低于30%的肾病患者。在导入期，通过适当的限盐饮食和/或抗高血压治疗，血压得到良好控制。然后，患者每周接受一次6000IU的Epo治疗，直到Ht升高5%。对于整个患者组，AGT基因多态性分析显示，31例（61%）为T235T（T/T），19例（37%）为M235T（M/T），1例（2%）为M235M（M/M）。在接受Epo治疗后，11例（22%）患者出现高血压（定义为平均血压升高超过10mmHg），所有这些患者均携带纯合T等位基因（T/T）。另一方面，未发生高血压的患者中T/T的频率为50%（T/T:T/M = 20:19例），差异有统计学意义（卡方检验p = .003）。估计与Epo诱导的高血压相关的变量依次为T等位基因、性别（男性）和Ht升高程度。我们的初步研究表明，携带两份T等位基因拷贝（即T纯合子）的个体在接受Epo治疗时极易发生高血压。这些结果表明，AGT T235变异体可能是Epo诱导的高血压发生的主要基因。
