Abstract P159: Genetic Variants of the Angiotensinogen Gene Predict Hypertension Incidence among Chinese Han Population: The GenSalt Study
The aim of this study is to comprehensively examine the association between genetic variants from the renin-angiotensin-aldosterone system (RAAS) and hypertension incidence among the participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study. The GenSalt study was initially conducted among Han Chinese in the north rural China during 2003-2005, and the follow-up studies were carried out in 2008-09 and 2011-12 with an average follow-up period of 7.5 years. A total of 2003 GenSalt participants without hypertension (defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg or taking antihypertensive medication) in the initial examination was included in this study. Nine BP measurements were obtained using a random-zero sphygmomanometer during a period of 3 days in both the initial study and the follow-up study. A total of 106 tagSNPs (minor allele frequencies ≥ 0.05) from 11 genes from the RAAS (REN, RENBP, AGT, ACE, AGTR1, AGTR2, CYP11B1, CYP11B2, HSD11B1, HSD11B2, and NR3C2) were genotyped using SNPlex assays. Additive associations between single SNPs and hypertension incidence were assessed using generalized estimating equation models accounting for the non-independence of family members. We identified multiple SNPs from the AGT (1 SNP), ACE (1 SNP), AGTR1 (3 SNPs), NR3C2 (1 SNP), and CYP11B1 (1 SNP) genes associated with hypertension incidence (all P < 0.05). Of them, the most significant variant is SNP rs2071405 (G/A; frequency of allele A, 0.17) from the angiotensinogen gene (AGT). After adjustment for age, gender, body mass index, and follow-up period, the minor A allele of rs2071405 was significantly associated with increased risk for hypertension development (P = 0.0003). The estimated hypertension incidences were 0.32, 0.37, and 0.49 for the GG, GA, and AA carriers, respectively. Using genotype GG carriers as the reference group, the relative risks (95% CI) of hypertension were 1.18 (1.02, 1.37) and 1.56 (1.31, 1.86) for GA and AA carriers, respectively. SNP rs2071405 is located at the promoter region of the AGT gene, predicted to be the binding sites for multiple transcription factors. After adjustment for multiple testing using the Bonferroni method, the association of this SNP with hypertension incidence remained significant. In conclusion, this study indicates that genetic variants from the RAAS may predict the development of hypertension. These finding may help improve the prediction and prevention of hypertension.
- © 2013 by American Heart Association, Inc.