*2.5. Other genes*

This section highlights several variants in genes that have been associated with hypertension in African Americans, which are also listed in Table 2.

#### 2.5.1. *GRK4*

G protein-coupled receptor kinases (GRKs) participate in the desensitization of G protein-coupled receptors, including D1 receptors, in the proximal renal tubules; variants in *GRK4* (4p16.3) were shown to improperly excrete sodium in rodents and humans with hypertension [104]. A recent report using genetic sequencing of genes implicated in sodium and water retention in African Americans revealed variants associated with amino acid changes were implicated with low renin resistant hypertension [105]. Three variants in *GRK4* (pR65L, p.A142V, and p. A486V) were 94.4% predictive of salt-sensitive hypertension. Additionally, the number of *GRK4* variants was inversely related to salt excretion [105], suggesting that *GRK4* is an important gene in the regulation of the hyporeninemic hypoaldosteronism phenotype in African Americans with hypertension. In this study, other variants that were reported in association with hypertension in the same population included *CYP11B2*, which encodes for aldosterone synthase.

#### 2.5.2. *SCG2*, *PHOX2A* and *PHOX2B*

Wen et al. reported on the association between a regulatory variant in secretogranin II (*SCG2*) in African Americans [96]. They sequenced the entire gene from 180 diverse ethnic group and showed that variant 736 was common among subjects of African descent. Two transactivating factors were identified, including ARIX (*PHOX2A*) and *PHOX2B*, while a positive selection of the protective allele within the human lineage was observed [96]. In another study, a single variant that converts methionine to threonine at amino acid 235 (M235T) of the angiotensinogen gene (*AGT*) was found to be associated with hypertension in Caucasians [106]. Kumar et al. reported an A/G polymorphism at position -217 of the *AGT* gene promoter and found that the frequency of allele A is increased in African Americans [97].
