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Ca-blockers
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No effect* on BP lowering efficacy [34, 40, 41, 43]
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1) Lower clearance nifedipine with African ancestry [46]
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1) Ancestry/age profiling superior to renin in predictingdrug response [38]
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2) CYP3A4 genotypes sooner at BPgoal†‡
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2) Ca-blockers effectively block enhanced Ca-dependentvascular contractility, potentially mediated by high CK/lowNO with African ancestry (Figure 2) [11, 12, 72]
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3) CYP3A5 genotypes not associated with BP response [17, 24]
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3) Pharmacogenomics: ACE G12269A, C17888T, andG20037A, and variants in the promoter region of theangiotensinogen gene (−217G = > A and–20A = > C), were not associated withBP response to respectively amlodipine and nifidipine [23, 26]
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Diuretics
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No effect on BP lowering efficacy [70]
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No differences found between ancestry groups [33]
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1) No association with plasma renin levels [57, 63, 65, 66], or ancestry/age better predictor of responsethan renin [15, 38]
|
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2) Diuretics effectively block enhanced sodium retention [86], potentially mediated by high CK in persons ofAfrican ancestry (Figure 3) [11, 12, 73, 87]
|
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3) Pharmacogenomics: greater BP response with AGT 6Aand AT1R 1166A alleles (only women); [30]GNB3T allele associated with greater BP response toHCT (only men); [32]ACE I/D, CYP11B2 C-344 T, RENA7174G [30], STK39[76], α-adducin Gly460Trp, ADRBK1, andGRK5 Gln41Leu [77] not associated with BP response
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ACE-i
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Lower efficacy with high salt [41]
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No association of BP response with CYP3A4 A392G,T16090C, or CYP3A5 A6986G genotypes [17]
|
1) Ancestry/age profiling superior to renin in predictingdrug response [38]
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2) Low NO bioavailability may attenuate response(Figure 2) [10, 12, 36, 37, 72, 79–81]
|
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3) Pharmacogenomics: ACE DD poorer response to lisinopril;[28]§ Homozygous ACE G12269A andC17888T faster on BP goal with ramipril than heterozygousgenotypes; [23] AA genotype 217G = > A and–20A= > C, promoter region of theangiotensinogen gene: no significant BP decrease withenalapril or lisinopril [26].
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β-Blockers
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No effect on BP lowering efficacy [70]
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No consistent differences between persons of African vsEuropean ancestry [44, 45, 52, 55, 56, 59, 61, 64],[67]
|
1) Ancestry/age profiling superior to renin in predictingdrug response [15, 38, 53]
|
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2) High vascular contractility may promote peripheralvasoconstriction with β-adrenergic blockers(Figure 2) [3, 11, 12, 72, 88–92]
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3) Pharmacogenomics: ADRB1 Arg 389/Ser 49 associateswith greater, or attenuated BP lowering; [14, 20, 74]GRK4 Ala142Val faster on BP goal with metoprolol(only men); [19]GRK4 Arg65Leu and Ala486Val, GRK5 andGRK2 genotypes not associated with BP response [18, 77]
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