|Title||Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Cunningham, PN, Wang, Z, Grove, ML, Cooper-Dehoff, RM, Beitelshees, AL, Gong, Y, Gums, JG, Johnson, JA, Turner, ST, Boerwinkle, E, Chapman, AB|
|Keywords||Adult, African Americans, Angiotensin II Type 1 Receptor Blockers, Apolipoprotein L1, Benzimidazoles, Female, Genome-Wide Association Study, Genotype, Humans, Hypertension, Male, Middle Aged, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Tetrazoles, Treatment Outcome|
BACKGROUND: Hypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease.
METHODS: AA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4-9 weeks of monotherapy with thiazides, beta blockers, or candesartan. APOL1 G1 and G2 variants were determined by direct sequencing or imputation.
RESULTS: Baseline systolic BP (SBP) and diastolic BP (DBP) levels did not differ based on APOL1 genotype. Subjects with 1-2 APOL1 risk alleles had a greater SBP response to candesartan (-12.2 +/- 1.2 vs -7.5 +/- 1.8 mmHg, p = 0.03; GERA2), and a greater decline in albuminuria with candesartan (-8.3 +/- 3.1 vs +3.7 +/- 4.3 mg/day, p = 0.02). APOL1 genotype did not associate with BP response to thiazides or beta blockers. GWAS was performed to determine associations with BP response to candesartan depending on APOL1 genotype. While no SNPs reached genome wide significance, SNP rs10113352, intronic in CSMD1, predicted greater office SBP response to candesartan (p = 3.7 x 10-7) in those with 1-2 risk alleles, while SNP rs286856, intronic in DPP6, predicted greater office SBP response (p = 3.2 x 10-7) in those with 0 risk alleles.
CONCLUSIONS: Hypertensive AAs without overt kidney disease who carry 1 or more APOL1 risk variants have a greater BP and albuminuria reduction in response to candesartan therapy. BP response to thiazides or beta blockers did not differ by APOL1 genotype. Future studies confirming this initial finding in an independent cohort are required.
|Alternate Journal||PLoS ONE|
|PubMed Central ID||PMC6750571|
|Grant List||UL1 RR029890 / RR / NCRR NIH HHS / United States |
UL1 RR025008 / RR / NCRR NIH HHS / United States
M01 RR000039 / RR / NCRR NIH HHS / United States
UL1 RR024150 / RR / NCRR NIH HHS / United States
UL1 TR000064 / TR / NCATS NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States
U01 GM074492 / GM / NIGMS NIH HHS / United States