Hunt S C, Cook N R, Oberman A, Cutler J A, Hennekens C H, Allender P S, Walker W G, Whelton P K, Williams R R
From Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City; the Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
Hypertension. 1998 Sep;32(3):393-401. doi: 10.1161/01.hyp.32.3.393.
The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2x2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval [0.87, 2.34], test for trend across all 3 genotypes, P=0.10). In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 [0.34, 0.98] versus usual care) but not for persons with the GG genotype (relative risk=1.2 [0.79, 1.81], test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17). Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension.
血管紧张素原基因已被证实与原发性高血压及血压升高有关。一种被认为与高血压易感性相关的功能性变异发生在该基因启动子区域的 -6 位，其中 A 对 G 的碱基对替换与较高的血管紧张素原水平相关。为了检验血管紧张素原基因内的一个等位基因是否与随后的高血压发病率以及对持续限钠的血压反应有关，对参与高血压预防试验第二阶段的 1509 名白人男性和女性受试者进行了血管紧张素原基因座的基因分型。参与者的舒张压在 83 至 89 mmHg 之间，并被随机分为 2×2 析因设计的限钠组、减重组、联合干预组或常规护理组。常规护理组中核苷酸位置 -6 处为 AA 基因型的人，其高血压 3 年发病率（44.6%）高于 GG 基因型的人（31.5%），相对风险为 1.4（95%置信区间[0.87, 2.34]，对所有 3 种基因型进行趋势检验，P = 0.10）。相比之下，限钠后 AA 基因型的人高血压发病率显著降低（相对风险 = 0.57[0.34, 0.98]，与常规护理相比），但 GG 基因型的人则不然（相对风险 = 1.2[0.79, 1.81]，趋势检验 P = 0.02）。限钠组与常规护理组相比，36 个月时舒张压的下降在所有 3 种基因型中呈现出显著趋势（P = 0.01），AA 基因型的人净血压下降幅度更大（-2.2 mmHg），而 GG 基因型的人则为（+1.1 mmHg）。3 种基因型在净收缩压下降方面（AA 为 -2.7 mmHg，GG 为 -0.2 mmHg）的类似趋势并不显著（P = 0.17）。减重对高血压发病率和血压下降影响的基因型趋势与限钠相似。我们得出结论，血管紧张素原基因型可能影响血压对限钠或减重的反应以及高血压的发生。
