Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension - Trials of hypertension prevention, phase II
Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension - Trials of hypertension prevention, phase II
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DOI：
10.1161/01.hyp.32.3.393
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发表时间：
1998-09-01
期刊：
影响因子：
8.3
通讯作者：
Williams, RR
中科院分区：
文献类型：
--
作者：
Hunt, SC;Cook, NR;Williams, RR
血管紧张素原基因与原发性高血压和血压升高有关。据信与高血压易感性有关的功能变体发生在该基因启动子区的-6位，其中A对G碱基对的取代与较高的血管紧张素原水平相关。为了检测血管紧张素原基因中的等位基因是否与随后的高血压发病率和对持续降钠的血压反应有关，对参加高血压预防试验II期的1509名白色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和89 mm Hg之间，并以2X2析因设计随机分配到钠减少组、体重减轻组、联合干预组或常规护理组。普通护理组中核苷酸-6位AA基因型者3年高血压发病率较高与GG基因型相比，（31.5%），相对危险度为1.4（95%置信区间[0.87，2.34]，所有3种基因型的趋势检验，P=0.10），相反，AA基因型人群减钠后高血压发病率显著降低（相对危险度=0.57 [0.34，0.98] vs常规治疗），但CG基因型患者则不然（相对危险度=1.2 [0.79，1.81]，趋势检验P=0.02）。与常规治疗相比，减钠组36个月时舒张压的下降在所有3种基因型中均显示出显著趋势（P=0.01），AA基因型（-2.2 mm Hg）的净血压下降幅度大于GG基因型（+1.1 mm Hg）。3种基因型之间净收缩压下降的类似趋势（AA为-2.7 mmHg，GG为-0.2 mmHg）并不显着（P=0.17），体重减轻对高血压发病率和血压下降的影响的基因型趋势与钠减少的趋势相似。我们的结论是，血管紧张素原基因型可能会影响血压反应钠或体重减轻和发展的高血压。
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 CG 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.