## 2 Precision Medicine and Cardiology
### Hypertension
#### 2.2.1 Hypertension Pharmacogenomics  
Genetic polymorphisms and response to diuretics: Current evidence identifies maximum target polymorphisms in response to thiazide diuretics. As opposed to the findings of the GenHAT study, the homozygous carriers of ACE I/D polymorphisms, ACE II, showed a small reduction in blood pressure response to hydrochlorothiazzide, compared to homozygous carriers of ACE DD alleles [72; 75]. Another study reported the response to thiazide diuretic in African Americans with SNP rs/297610 CC located on chromosome 12q15 [76]. Other genetic association studies showed that PRKCAA allele carriers had a better blood pressure response than GG homozygote patients. Another study targeting the UMOD gene polymorphism showed differential BP response to loop diuretics in hypertenusives. They divided patients into two groups: 1. UMOD group (AA genotype), which showed a good response to loop diuretics, and 2. \"Low\" UMOD group, which exhibited a lower BP response to loop diuretics [70]. Genetic polymorphisms and response to other antihypertenusives: Blood pressure regulation in humans involves at least 70 genes and presents with a complex set of individual differences. The human beta (1)-adrenergic receptor (ADRB1) has two common  
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\begin{tabular}{p{14.2 pt} p{142.3 pt} p{142.3 pt} p{142.3 pt} p{142.3 pt} p{142.3 pt}} \hline \hline
**S.N. ** & **Authors** & **Year** & **Study Design** & **Clinically Relevant Findings** & **Comments** & **References** \\ \hline \hline \multirow{18}{*}{18} & \multirow{8}{*}{[PERSON] et al.} & \multirow{12}{*}{2013} & \multirow{8}{*}{Meta-Analysis} & \multirow{8}{*}{ADDI and ACE I/D polymorphisms’ role in HCT response.} & \multirow{8}{*}{ADDI polymorphism} & \multirow{8}{*}{ADDI polymorphism} \\  & & & & & & \\ \cline{4-7}  & & & & & & \\ \cline{4-7}  & & & & & & \\ \hline \multirow{18}{*}{19} & \multirow{8}{*}{[PERSON] et al.} & \multirow{12}{*}{2012} & \multirow{8}{*}{Original Study} & \multirow{12}{*}{PRKCA and GNAS-EDN3 in response to thiazide.} & \multirow{8}{*}{DRKCA and GNAS-EDN3 in Acditionally, GNAS-EDN3} & \multirow{8}{*}{DRKCA and GNAS-EDN3 in Acditionally, GNAS-EDN3} & \multirow{8}{*}{DRKCA and GNAS-EDN3 in Acditionally, GNAS-EDN3} & \multirow{8}{*}{DRKCA and GNAS-EDN3 in Acditionally, GNAS-EDN3} & \multirow{8}{*}{DRKCA and GNAS-EDN3 in Acditionally, GNAS-EDN3} & \multirow{8}{*}{DRKCA and GNAS-EDN3 infunctional polymorphisms (Ser49 Gly and Gly389 Arg), which are associated with varied responses to metoprolol in essential hypertension. Furthermore, 49 Ser389 Arg/49 Ser389 Arg and 49 Ser389 Arg/49 Gly389 Arg polymorphisms have been seen as good responders, whilst 49 Ser389 Gly/49 Gly389 Arg and 49 Ser389 Gly/49 Ser389 Gly polymorphisms have been seen to be non-responders [77]. ADRB1 polymorphisms further revealed that C allele homozygotes showed a better response to metoprolol than G allele carriers [78]. Another study reported a possible link between nephrin (NPNS1) gene variants and a good response to the angiotensin receptor antagonist, losartan, in hypertensive patients [79]. Other less commonly studied genetic polymorphisms include GRK4 polymorphisms, namely R65L, A142V, and A486V. Studies have revealed that homozygote double variants of 65 L and 142 V require more aggressive antihypertensive therapy than the homozygous single variants or heterozygous carriers to achieve a target mean arterial blood pressure [71]. Another study aimed at finding rare and common variants associated with hypertension identified 31 novel genetic regions--rare missense variants in RBM47, COL21A1, and RRAS [67]. These allelic variations can lay the foundation for newer drug targets. Furthermore, by using polygenic risk score (based on the total number of genetic loci required to be assessed to estimate the risk of developing a disease), five potential loci (PKD2L1, SLC12A2, CACNA1C, CACNB4, and CA7) have been reported as novel therapeutic targets for hypertensive therapy.