Key result
Several genetic loci showed suggestive interactions with loop diuretic use for systolic and diastolic blood pressure, although no single nucleotide polymorphism reached genome-wide significance.
Why the study?
Does loop diuretic use interact with specific genetic variants to affect systolic and diastolic blood pressure in African American and European American populations?
Observational (n=2,453)
Yes
Does loop diuretic use interact with specific genetic variants to affect systolic and diastolic blood pressure in African American and European American populations?
This study identified several candidate genes that may modulate blood pressure response to loop diuretics differently across ethnic groups, providing prioritized SNPs for future pharmacogenomic studies in hypertension.
Suggestive loci should not alter loop diuretic prescribing; leaves open prioritized SNPs for replication in hypertension pharmacogenomics.
Blood pressure (BP) is significantly influenced by genetic factors; however, less than 3% of the BP variance has been accounted for by variants identified from genome-wide association studies (GWAS) of primarily European-descent cohorts. Other genetic influences, including gene-environment (GxE) interactions, may explain more of the unexplained variance in BP. African Americans (AA) have a higher prevalence and earlier age of onset of hypertension (HTN) as compared with European Americans (EA); responses to anti-hypertensive drugs vary across race groups. To examine potential interactions between the use of loop diuretics and HTN traits, we analyzed systolic (SBP) and diastolic (DBP) blood BP from 1222 AA and 1231 EA participants in the Hypertension Genetic Epidemiology Network (HyperGEN). Population-specific score tests were used to test associations of SBP and DBP, using a panel of genotyped and imputed single nucleotide polymorphisms (SNPs) for AA (2.9 million SNPs) and EA (2.3 million SNPs). Several promising loci were identified through gene-loop diuretic interactions, although no SNP reached genome-wide significance after adjustment for genomic inflation. In AA, SNPs in or near the genes NUDT12, CHL1, GRIA1, CACNB2, and PYHIN1 were identified for SBP, and SNPs near ID3 were identified for DBP. For EA, promising SNPs for SBP were identified in ESR1 and for DBP in SPATS2L and EYA2. Among these SNPs, none were common across phenotypes or population groups. Biologic plausibility exists for many of the identified genes, suggesting that these are candidate genes for regulation of BP and/or anti-hypertensive drug response. The lack of genome-wide significance is understandable in this small study employing gene-drug interactions. These findings provide a set of prioritized SNPs/candidate genes for future studies in HTN. Studies in more diversified population samples may help identify previously missed variants.
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Fuentes et al. (2013) conducted an observational in Hypertension (n=2,453). Loop diuretic use and SNP interaction vs. Non-use of loop diuretics was evaluated on Association of SNP-loop diuretic interaction with systolic and diastolic blood pressure. Several genetic loci showed suggestive interactions with loop diuretic use for systolic and diastolic blood pressure, although no single nucleotide polymorphism reached genome-wide significance.
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