Key result
The G allele of SNP rs3784921 was associated with higher baseline plasma renin activity (β=0.47; P=2.09×10−6) and smaller systolic blood pressure reduction in response to hydrochlorothiazide.
Why the study?
Do specific genetic variants influence baseline plasma renin activity and blood pressure response to antihypertensive drugs in hypertensive patients?
Observational (n=758)
Do specific genetic variants influence baseline plasma renin activity and blood pressure response to antihypertensive drugs in hypertensive patients?
Effect estimate: β=0.47
p-value: p=2.09×10−6
Specific genetic variants, such as rs3784921 in the SNN-TXNDC11 region, are associated with baseline plasma renin activity and influence blood pressure response to hydrochlorothiazide, providing pharmacogenomic insights into hypertension management.
rs3784921 may inform hydrochlorothiazide response; hypothesis-generating for pharmacogenomic hypertension trials.
Background: Plasma renin is an important regulator of blood pressure (BP). Plasma renin activity (PRA) has been shown to correlate with variability in BP response to antihypertensive agents. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive Responses). Methods: Multiple linear regression analysis was performed in 461 whites and 297 blacks using an additive model, adjusting for age, sex, and ancestry-specific principal components. Top SNPs were prioritized by testing the expected direction of association for BP response to atenolol and hydrochlorothiazide. Top regions from the BP response prioritization were tested for functional evidence through differences in gene expression by genotype using RNA sequencing data. Regions with functional evidence were assessed for replication with baseline PRA in an independent study (PEAR-2). Results: Our top SNP rs3784921 was in the SNN-TXNDC11 gene region. The G allele of rs3784921 was associated with higher baseline PRA (β=0.47; P =2.09×10 −6 ) and smaller systolic BP reduction in response to hydrochlorothiazide (β=2.97; 1-sided P =0.006). In addition, TXNDC11 expression differed by rs3784921 genotype ( P =0.007), and rs1802409, a proxy SNP for rs3784921 ( r 2 =0.98–1.00), replicated in PEAR-2 (β=0.15; 1-sided P =0.038). Additional SNPs associated with baseline PRA that passed BP response prioritization were in/near the genes CHD9, XIRP2, and GHR. Conclusions: We identified multiple regions associated with baseline PRA that were prioritized through BP response signals to 2 mechanistically different antihypertensive drugs. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00246519.
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McDonough et al. (2018) conducted an observational in Hypertension (n=758). rs3784921 G allele was evaluated on Baseline plasma renin activity (PRA) (β=0.47, p=2.09×10−6). The G allele of SNP rs3784921 was associated with higher baseline plasma renin activity (β=0.47; P=2.09×10−6) and smaller systolic blood pressure reduction in response to hydrochlorothiazide.
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