A study of AGT as a susceptibility gene for hypertension in the Saudi population

The renin‐angiotensin system is the core regulator of systemic blood pressure. A constituent of this system is angiotensigen (AGT), a serum rennin substrate glycoprotein synthesized in the liver, which is released as the precursor of angiotensin, the hormone that forms part of the systemic blood pressure regulatory system. Accordingly, mutations in the AGT gene are likely to lead to blood pressure disorders. In order to evaluate the role of this gene in primary hypertension, we first sequenced the AGT gene in 200 Saudi individuals to determine the variants of interest, leading to the discovery of >30 SNPs with minor allele frequency of >0.10. In the present study, we performed association study for 3 of these variants (rs214858C>T, rs5051A>G and rs3789679C>T) in 3246 hypertensive cases versus 1001 controls all of Saudi origin by the Applied Biosystems real‐time PCR procedure. Of these variants, rs5051 [Odds ratio(95% Confidence Interval = 1.14(1.01–1.31); p=0.035] conferred risk for HTN. This association appeared to follow a dominant model [1.39(1.11–1.76); p=0.005] of inheritance. Interestingly the same variant was also associated with coronary artery disease within the same population, but not myocardial infarction, type 2 diabetes, or hyperlipidaemia. The results indicate the rs5051 which resides in the 5′ UTR of the AGT gene is a susceptibility variant for hypertension in the Saudi population.