Department of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Hypertens. 2010 Dec;28(12):2422-8. doi: 10.1097/HJH.0b013e32833ea74e.
The purpose of this study was to examine the association between genetic variants in the renin-angiotensin system and blood pressure (BP) responses to the cold pressor test (CPT).
The CPT was conducted among 1998 Han Chinese participants. BP measurements were obtained before and after the CPT using a standard sphygmomanometer according to a standard protocol. The association between SNP genotypes and BP responses to the CPT was assessed using a mixed linear model.
Of 68 SNPs genotyped in six renin-angiotensin system genes, two were strongly associated with DBP responses to CPT (P ≤ 0.001; false discovery rate q value < 0.05): rs2006765 and rs943580 in the angiotensinogen (AGT) gene. Compared to C allele carriers of rs2006765, the TT homozygotes had a significantly decreased DBP response to the CPT. For participants with the TT genotype, percentage DBP responses were 5.68% (4.25-7.10%), compared to corresponding responses of 9.17% (8.66-9.68%) among participants with the CC+CT genotype. In addition, SNP rs4681443 of the angiotensin type 1 receptor (AGTR1) gene was significantly associated with percentage SBP responses to CPT (P ≤ 0.001; q-value <0.05).
Briefly, our study identified variants in the AGT and AGTR1 genes that may influence BP responses to CPT in the Han Chinese population. These results show that genetic variants in the renin-angiotensin system play an important role in BP responses to CPT and, therefore, in predicting future hypertension.
本研究旨在探讨肾素-血管紧张素系统(renin-angiotensin system,RAS)中的遗传变异与冷加压试验(cold pressor test,CPT)血压(blood pressure,BP)反应之间的关联。
本研究纳入了 1998 名汉族参与者进行 CPT。按照标准方案,使用标准血压计在 CPT 前后测量 BP。采用混合线性模型评估 SNP 基因型与 CPT 后 BP 反应之间的关联。
在六个 RAS 基因中,对 68 个 SNP 进行基因分型,有两个 SNP 与 CPT 后舒张压(diastolic blood pressure,DBP)反应强烈相关(P≤0.001;假发现率 q 值<0.05):血管紧张素原(angiotensinogen,AGT)基因中的 rs2006765 和 rs943580。与 rs2006765 的 C 等位基因携带者相比,TT 纯合子的 CPT 后 DBP 反应明显降低。对于 TT 基因型的参与者,DBP 反应的百分比为 5.68%(4.25-7.10%),而 CC+CT 基因型的相应反应百分比为 9.17%(8.66-9.68%)。此外,血管紧张素 1 型受体(angiotensin type 1 receptor,AGTR1)基因中的 SNP rs4681443 与 CPT 后收缩压(systolic blood pressure,SBP)的百分比反应显著相关(P≤0.001;q 值<0.05)。
总之,我们的研究在汉族人群中发现了 AGT 和 AGTR1 基因中的变异,这些变异可能影响 CPT 时的 BP 反应。这些结果表明,RAS 中的遗传变异在 CPT 时的 BP 反应中起重要作用,因此在预测未来高血压方面具有重要意义。