血管紧张素原（ACE）基因多态性与原发性高血压及降压药物疗效相关性的研究进展
Association of genetic variants in the apelin-APJ system and ACE2 with blood pressure responses to potassium supplementation: the GenSalt study.
机构信息
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
出版信息
Am J Hypertens. 2010 Jun;23(6):606-13. doi: 10.1038/ajh.2010.36. Epub 2010 Mar 11.
BACKGROUND
Genetic factors may influence blood pressure (BP) responses to dietary potassium intake. We examined the association of genetic variants in the apelin-APJ system and angiotensin-converting enzyme 2 (ACE2) with BP responses to potassium supplementation.
METHODS
We conducted a 7-day potassium supplementation (60 mmol/day) intervention among 1,906 Chinese adults who participated in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Tag single-nucleotide polymorphisms (SNPs) based on HapMap data and potential functional SNPs were selected in the APLN, APLNR, and ACE2 genes. Because the ACE2 and APLN genes are located on the X chromosome, men and women were analyzed separately.
RESULTS
In women, SNP rs2235306 in the APLN gene was significantly associated with diastolic BP (DBP) response to potassium supplementation (P = 0.0009). The DBP responses (95% confidence interval (CI)) among those with genotypes T/T, T/C, and C/C were -2.22 (-2.74, -1.70), -1.69 (-2.20, -1.19), and -0.81 (-1.54, -0.09) mm Hg, respectively. In men, SNP rs4646174 of the ACE2 gene was significantly associated with systolic BP (SBP), DBP, and mean arterial pressure (MAP) responses to potassium supplementation (P = 0.0001, P = 0.001, and P = 3.0 x 10(-6), respectively). The SBP, DBP, and MAP responses (95% CI) were -0.79 (-2.27, 0.69) vs. -3.53 (-3.94, -3.12), 1.07 (-0.34, 2.49) vs. -1.06 (-1.43, -0.69), and 0.44 (-0.60, 1.48) vs. -1.89 (-2.22, -1.55) mm Hg among men with minor G allele compared to those with major C allele of rs4646174, respectively.
CONCLUSION
Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.
背景
遗传因素可能会影响血压（BP）对膳食钾摄入的反应。我们研究了 Apelin-APJ 系统和血管紧张素转换酶 2（ACE2）的基因变异与钾补充后 BP 反应之间的关联。
方法
我们在中国参加遗传流行病学盐敏感性网络（GenSalt）研究的 1906 名成年人中进行了为期 7 天的钾补充（60mmol/天）干预。根据 HapMap 数据选择 Apelin-APJ 系统和 ACE2 基因中的标签单核苷酸多态性（SNP）和潜在功能 SNP。由于 ACE2 和 Apelin 基因位于 X 染色体上，因此分别对男性和女性进行分析。
结果
在女性中，Apelin 基因中的 SNP rs2235306 与钾补充后舒张压（DBP）反应显著相关（P=0.0009）。基因型为 T/T、T/C 和 C/C 的个体的 DBP 反应（95%置信区间（CI））分别为-2.22（-2.74，-1.70）、-1.69（-2.20，-1.19）和-0.81（-1.54，-0.09）mmHg。在男性中，ACE2 基因中的 SNP rs4646174 与 SBP、DBP 和平均动脉压（MAP）对钾补充的反应显著相关（P=0.0001、P=0.001 和 P=3.0×10(-6)，分别）。SBP、DBP 和 MAP 反应（95%CI）分别为-0.79（-2.27，0.69）与-3.53（-3.94，-3.12）、1.07（-0.34，2.49）与-1.06（-1.43，-0.69）和 0.44（-0.60，1.48）与-1.89（-2.22，-1.55）mmHg，与携带次要 G 等位基因的个体相比，携带主要 C 等位基因的个体。
结论
我们的研究表明，Apelin 和 ACE2 的遗传变异可能会影响钾摄入对 BP 的反应。
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