학술논문
Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry
Document Type
Article
Author
Irvin, Marguerite; Sitlani, Colleen; Noordam, Raymond; Avery, Christie; Bis, Joshua; Floyd, James; Li, Jin; Limdi, Nita; Srinivasasainagendra, Vinodh; Stewart, James; Mutsert, Renée; Mook-Kanamori, Dennis; Lipovich, Leonard; Kleinbrink, Erica; Smith, Albert; Bartz, Traci; Whitsel, Eric; Uitterlinden, Andre; Wiggins, Kerri; Wilson, James; Zhi, Degui; Stricker, Bruno; Rotter, Jerome; Arnett, Donna; Psaty, Bruce; Lange, Leslie
Source
The Pharmacogenomics Journal; February 2019, Vol. 19 Issue: 1 p97-108, 12p
Subject
Language
ISSN
1470269X; 14731150
Abstract
We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N= 4835) and four African-ancestry (AA) cohorts (N= 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P< 5 × 10−8) for SNP-ACE-I/ARB interactions on serum K+ that were located between NR2F1-AS1and ARRDC3-AS1on chromosome 5 (top SNP rs6878413 P= 1.7 × 10−8; ratio of serum K+ in ACE-I/ARB exposed compared to unexposed is 1.0476, 1.0280, 1.0088 for the TT, AT, and AA genotypes, respectively). Trans-ethnic fine mapping identified the same group of SNPs on chromosome 5 as genome-wide significant for the ACE-I/ARB analysis. In conclusion, SNP-by-ACE-I /ARB interaction analyses uncovered loci that, if replicated, could have future implications for the prevention of arrhythmias due to anti-HTN treatment-related hyperkalemia. Before these loci can be identified as clinically relevant, future validation studies of equal or greater size in comparison to our discovery effort are needed.