Abstract
We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a β-blocker-based strategy (β-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP∗treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis P=5.3 × 10 ' ' 8). rs11124945 G allele carriers had lower odds for NOD when exposed to the β-blocker strategy compared with the CCB strategy (Odds ratio OR=0.38(0.24' '0.60), P=4.0 × 10 ' ' 5), whereas A/A homozygotes exposed to the β-blocker strategy had increased odds for NOD compared with the CCB strategy (OR=2.02(1.39' '2.92), P=2.0 × 10 ' ' 4). eQTL annotation of the 2p21 locus provides functional support for regulating gene expression.
Original language | English |
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Pages (from-to) | 106-112 |
Number of pages | 7 |
Journal | Pharmacogenomics Journal |
Volume | 18 |
Issue number | 1 |
DOIs | |
Publication status | Published - 01-01-2018 |
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Genetics
- Pharmacology