Table 2 GRK4 variants in hypertensive and normotensive subjects
GRK4 Variant | Ethnic Group | Single or Multilocus Analyses | Clinical Findings |
|---|---|---|---|
A142V (rs1024323) | Japanese | Single-locus | Correlates with low-renin hypertension [99] |
Japanese | Two-locus | The combination of GRK4 A142V and CYP11B2 predicts low-renin essential hypertension [99] | |
Japanese | Multi-locus | The combination of GRK4 A142V, R65L, and A486V predicts salt-sensitive hypertension [99] | |
African- American | Single-locus | Correlates with blood pressure response to metoprolol among hypertensive male subjects [111] | |
Black subjects | Single-locus | Predicts blood pressure response to dietary modification in Black subjects with mild-to-moderate hypertension [169] | |
American | Single-locus | Correlates with increased risk for adverse cardiovascular outcomes [164] | |
Japanese | Single-locus | Correlates with hypertension; Carriers of hGRK4 142V have a greater decrease in SBP in response to ARBs [165] | |
Chinese | Single-locus | Hypertensive subjects with GRK4 A142V are more likely to be non-dippers [166] | |
A486V (rs1801058) | Italian | Single-locus | Associates with mild hypertension [102] |
Euro-Australian | Single-locus | Correlates with hypertension [101] | |
Chinese | Single-locus | Associates with mild hypertension [100] | |
Chinese | Single-locus | Correlates with hypertension [171] | |
African American | Single-locus | Negatively correlates with hypertension in nonobese subjects [112] | |
European | Single-locus | Correlates with salt sensitivity of blood pressure [107] | |
African Brazilian | Two-locus | NOS3-GRK4 interaction is related to DBP levels [98] | |
American | Single-locus | Correlates with increased risk for adverse cardiovascular outcomes [164] | |
Japanese | Single-locus | Correlates with hypertension; Carriers of hGRK4 486V were less to achieve the blood pressure goal in response to an ARB [165] | |
Korean | Single-locus | A high sodium intake increases the obesity risk in children with GRK4 A486V regardless of sex [116] | |
Korean | Multi-locus | A high sodium intake increases the obesity risk in boys with the combination of GRK4 A486V, ACE, and SLC12A3 variants [116] | |
Korean | Two-locus | The combination of GRK4 A486V and CYP11B2 variants increases the obesity risk in girls when sodium intake is increased [116] | |
Chinese | Single-locus | Hypertensive subjects with GRK4 A486V are more likely to be non-dippers [166] | |
R65L (rs2960306) | Ghanaian | Two-locus | The combination of GRK4 R65L and ACE predicts the hypertensive phenotype [108] |
American | Single-locus | Associates with stress-induced reduction in urinary sodium excretion in Black normotensive adolescents [117] | |
Black subject | Single-locus | Predicts positive blood pressure response to dietary modification in Black subjects with mild-to-moderate hypertension [169] | |
American | Single-locus | Correlates with increased risk for adverse cardiovascular outcomes [164] | |
Swiss | Two-locus | Patients with GRK4 65L and 142 V need more antihypertensive treatment to reach the same MAP than homozygous carriers of only 1 variant or heterozygous/wild-type carriers of R65L, A142V, and A486V alleles [168] | |
Korean | Single-locus | The GRK4 65 L TT genotype is inversely correlated with hypertension risk [103] | |
Chinese | Single-locus | Hypertensive subjects with GRK4 R65L are more likely to be non-dippers [166] | |
Other GRK4 variants | |||
rs2488815 | Chinese | Single-locus | Associates with the decreased eGFR [172] |
rs1419044 | American | Single-locus | Correlates with bevacizumab-induced hypertension [173] |
rs1557213 | Chinese | Single-locus | Contributes to the risk of hypertension [105] |
rs1644731 | Chinese | Two-locus | GRK4 rs1644731 and RDH8 rs1801058 are associated with hypertension [104] |
