***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were r and omly allocated to first-line treatment with a calcium channel blocker ( CCB ) , angiotensin-converting enzyme inhibitor ( ACEI ) or angiotensin II receptor blocker ( ARB ) . METHODS We recruited 265 ( 93 for CCB , 71 for ACEI and 101 for ARB ) patients who completed the genomic study .  Home blood pressure was measured for 5 days off-treatment before r and omization and for 5 days after 2 - 4 weeks of r and omized drug treatment . Genotyping was performed by 500 K DNA microarray chips . The blood pressure responses to the three drugs were analyzed separately as a quantitative trait . For replication of SNPs with p < 10(-4 ) , we used the multicenter GEANE study , in which patients were r and omized to valsartan or amlodipine . RESULTS SNPs in PICALM , TANC2 , NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication . CONCLUSION Our approach , the first based on high-fidelity phenotyping by home blood pressure measurement , might be a step in moving towards the personalized treatment of hypertension BACKGROUND African Americans have a disproportionate burden of hypertension and comorbid disease . Pharmacogenetic markers of blood pressure response have yet to be defined clearly . This study explores the association between G-protein-coupled receptor kinase type 4 ( GRK4 ) variants and blood pressure response to metoprolol among African Americans with early hypertensive nephrosclerosis . METHODS Participants from the African American Study of Kidney Disease and Hypertension ( AASK ) trial were genotyped at three GRK4 polymorphisms : R65L , A142V , and A486V . A Cox proportional hazards model , stratified by gender , was used to determine the relationship between GRK4 variants and time to reach a mean arterial pressure ( MAP ) of 107 mm Hg , adjusted for other predictors of blood pressure response . Potential interactions between the three polymorphisms were explored by analyzing the effects of gene haplotypes and by stratifying the analysis by neighboring sites . RESULTS The hazard ratio with 95 % confidence interval by A142V among men r and omized to a usual MAP ( 102 - 107 mm Hg ) was 1.54 ( 1.11 - 2.44 ; P = 0.0009 ) . The hazard ratio by A142V with R65/L65 or L65/L65 was 2.14 ( 1.35 - 3.39 ; P = 0.001 ) . Haplotype analyses were consistent but inconclusive . There was no association between A142V and blood pressure response among women . CONCLUSIONS Results suggest a sex-specific relationship between GRK4 A142V and blood pressure response among African-American men with early hypertensive nephrosclerosis . Men with a GRK4 A142 were less responsive to metoprolol if they had a GRK4 L65 variant . The effect of GRK4 variants and blood pressure response to metoprolol should be studied in larger clinical trials Abstract In previous studies , we found an endothelial nitric oxide synthase gene ( NOS3 ) variant rs2070744 associated with the ambulatory blood pressure ( BP ) response following bouts of moderate and vigorous intensity acute exercise , termed post‐exercise hypotension ( PEH ) . In a validation cohort , we sequenced NOS3 exons for associations with PEH . Obese ( 30.9 ± 3.6 kg.m−2 ) African American ( n = 14 ) [ AF ] and Caucasian ( n = 9 ) adults 42.0 ± 9.8 years with hypertension ( 139.8 ± 10.4/84.6 ± 6.2 mmHg ) performed three r and om experiments : bouts of vigorous and moderate intensity cycling and control . Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit . Variant genotypes were coded as number of minor alleles ( # MA ) and selected for additional statistical analysis based upon Bonferonni or Benjamini – Yekutieli multiple testing‐corrected P‐values under time‐adjusted linear models for 19 hourly BP measurements for each subject . After vigorous intensity over 19 h , among NOS3 variants passing multiple testing thresholds , as the # MA increased in rs891512 ( P = 6.4E‐04 ) , rs867225 ( P = 6.5E‐04 ) , rs743507 ( P = 2.6E‐06 ) , and rs41483644 ( P = 2.4E‐04 ) , systolic ( SBP ) decreased from 17.5 to 33.7 mmHg ; and in rs891512 ( P = 9.7E‐05 ) , rs867225 ( P = 2.6E‐05 ) , rs41483644 ( P = 1.6E‐03 ) , rs3730009 ( P = 2.6E‐04 ) , and rs77325852 ( P = 5.6E‐04 ) , diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only . In contrast , after moderate intensity over 19 h in NOS3 rs3918164 , as the # MA increased , SBP increased by 16.6 mmHg ( P = 2.4E‐04 ) among AF only . NOS3 variants exhibited associations with PEH after vigorous , but not moderate intensity exercise among AF only . NOS3 should be studied further for its effects on PEH in a large , ethnically diverse sample of adults with hypertension to confirm our findings Aim : To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients . Methods : One hundred sixty two Chinese Han hypertensive patients were administered iptakalim ( 5 or 10 mg/d , po ) for 8 weeks . Before the treatment and 24 h after completing the treatment blood pressure ( BP ) was measured . Genotyping was performed using direct sequencing . Results : Four common A190A , E23 K , I337V and 3′UTR + 62 G/A polymorphisms were found in KCNJ11 . The E23 K , I337V and 3′UTR + 62 G/A polymorphisms were in complete linkage disequilibrium , and I337V was used as a representative . There were no significant differences in age , body mass index , sex , baseline systolic BP ( SBP ) and diastolic BP ( DBP ) among the 3 genotypes for the four polymorphisms . Significant association was found between SBP response and the polymorphisms ( adjusted regression coefficient : 3.5 [ 1.2 ] mmHg ; P=0.003 for the A190A polymorphism ; adjusted regression coefficient : 3.1 [ 1.2 ] mmHg ; P=0.012 for the I337V polymorphism ) . The patients with TT genotype for A190A polymorphism had higher clinical efficacy than those with CC genotype . Conclusion : The results suggest the KCNJ11 polymorphisms are associated with the SBP-lowering response of short-term iptakalim therapy in Chinese Han hypertensive patients Background The pharmacokinetics ( PKs ) and pharmacodynamics ( PDs ) of telmisartan varies among the individuals , and the main causes remain unknown . The aim of this study was to evaluate the impact of ORM1 , as well as ABCC2 , ABCB1 , ABCG2 and SLCO1B3 polymorphisms , on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males . Method A total of 48 healthy males were included in this trial . Every volunteer ingested a single dose of 40 mg telmisartan , and the plasma drug concentration and blood pressure ( BP ) were measured up to 48 h. Result In this study , the area under the plasma concentration-time curve ( AUC ) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes , AUC(0–48 ) ( 113AA vs. 113AG , 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml , P = 0.033 ) , AUC(0–∞ ) ( 113AA vs. 113AG , 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml , P = 0.016 ) , and the change(% ) of the diastolic blood pressure ( DBP ) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan ( P = 0.026 ) . This study also showed that the allele of ABCC2 C3972 T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug . However , the common SNPs of ABCG2 C421 , ABCB1 C3435 T , and SLCO1B3 T334 G showed no impacts on the PKs of telmisartan or BP change(% ) in our trial . Conclusion The ORM1 A113 G polymorphism was associated with the PKs variability after taking telmsiartan , as well as ABCC2 C3972 T . The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(% ) from the baseline compared with the wild-type . Trial Registration Chinese Clinical Trial Registry Objective Regulators of G-protein signaling protein 2 ( RGS2 ) play an irreplaceable role in the control of normal blood pressure ( BP ) . One RGS2 ( -391 , C > G ) genetic variation markedly changes its mRNA expression levels . This study explored the relationship between this genetic variation and the responses to antihypertensive drugs in Chinese patients with essential hypertension . Methods Genetic variations of RGS2 were successfully identified in 367 specimens using polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) assays . All patients were treated with conventional doses of antihypertensives after a 2-week run-in period and followed-up according to our protocol . A general linear model multivariate analysis of variance ( ANOVA ) was used for the data analysis . Results A significant difference in the mean systolic BP change was observed between RGS2 ( -391 , C > G ) CC/CG ( n = 82 ) and GG ( n = 38 ) genotype carriers ( -13.6 vs. -19.9 mmHg , P = 0.043 ) who were treated with c and esartan , irbesartan or imidapril at the end of 6 weeks . In addition , the patients ’ BP responses to α , β-adrenergic receptor blockers exhibited an age-specific association with the RGS2 ( -391 , C > G ) genetic variation at the end of 4 weeks . Conclusion The RGS2 ( -391 , C > G ) genetic polymorphism may serve as a biomarker to predict a patient ’s response to antihypertensive drug therapy , but future studies need to confirm this A recent genome-wide analysis discovered an association between a haplotype ( from rs317689/rs315135/rs7297610 ) on Chromosome 12q15 and blood pressure response to hydrochlorothiazide ( HCTZ ) in African – Americans . Our aim was to replicate this association and investigate possible functional mechanisms . We observed similar associations between this haplotype and  HCTZ response in an independent sample of 746 Caucasians and African – Americans r and omized to HCTZ or atenolol treatment . The haplotype association was driven by variation at rs7297610 , where C/C genotypes were associated with greater mean ( systolic : 3.4 mmHg , P=0.0275 ; diastolic : 2.5 mmHg , P=0.0196 ) responses to HCTZ vs T-allele carriers . Such an association was absent in atenolol-treated participants , supporting this as HCTZ specific . Expression analyses in HCTZ-treated African – Americans showed differential pre-treatment leukocyte YEATS4 expression between rs7297610 genotype groups ( P=0.024 ) , and reduced post-treatment expression in C/C genotypes ( P=0.009 ) , but not in T-carriers . Our data confirm previous genome-wide findings at 12q15 and suggest differential YEATS4 expression could underpin rs7297610-associated HCTZ response variability , which may have future implication s for guiding thiazide treatment Abstract We found variants from the Angiotensinogen‐Converting Enzyme ( ACE ) , Angiotensin Type 1 Receptor ( AGTR1 ) , Aldosterone Synthase ( CYP11 
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Conclusions : Deep-sequencing the exons of this systematic ally assembled signature of genes represents a cost and time efficient approach to investigate the genomic basis for the antihypertensive effects of exercise