salt intake and genotyping for polymorphisms in the endothelial nitric oxide synthase (eNOS) gene, implicated in coronary artery disease and MI, to examine risk for hypertension in 281 healthy Japanese men. This study identified a specific mutation in the eNOS gene that, with a high-salt diet, was associated with a significant increase in blood pressure among affected men.
Zhang et al. (2010), in a small (n=329) cross-sectional study, identified the presence of cytochrome P450 3A polymorphisms in a group of Japanese adults. Blood pressure response to sodium intake, estimated by spot analysis of 24-hour urinary sodium excretion, was found to be associated with the frequency of expression of two allelic variants: a heterozygous modifier of blood pressure, and a homozygous variant in carriers that resulted in greater sensitivity to salt intake compared to noncarriers.
A small intervention study in 39 healthy adults in Sweden examined the influence of genetic variants in RAAS following a protocol of 4 weeks on a high-salt intake followed by 4 weeks on a low-salt intake (Dahlberg et al., 2007). Blood pressure measurements and 24-hour sodium excretions, taken at baseline and at the end of each dietary intervention, suggested enhanced salt sensitivity in normotensive participants carrying two variants of a gene associated with monogenic hypertension.
Kelly et al. (2009) and Gu et al. (2010) examined data from GenSalt, a large (n=1,906) 14-day intervention study carried out in rural China between 2003 and 2005, to identify gene variants that function in blood pressure regulation associated with salt sensitivity in a population consuming high levels of salt. Study participants consumed a low-sodium (3,000 mg per day) diet for the first 7 days, followed by a high-sodium (18,000 mg per day) diet for 7 days. Three timed urinary specimens were collected, one at baseline, then at the end of each intervention phase. Blood pressure measures were taken and genotyping for genetic polymorphisms was conducted for each participant. Kelly et al. (2009) identified two variants, one in the alpha-adducin gene and one in the guanine nucleotide binding protein beta polypeptide 3 genes. Gu et al. (2010) identified three novel variants from 11 RAAS candidate genes that were significantly associated with blood pressure response to salt intake. Another GenSalt study (Zhao et al., 2010) identified genetic variants in the angiotensin-converting enzyme 2 (ACE-2), a regulator of RAAS and the apelin receptor (a substrate of ACE-2), which were associated with blood pressure response to salt intake.
Together, these studies illustrate that a number of genetic variants are associated with salt sensitivity and susceptibility to high blood pressure associated with sodium intake, particularly among certain population subgroups. Additionally, individuals not seen to be at risk of hypertension may carry genetic polymorphisms that render them salt sensitive.