Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes
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...
Saved in:
Published in | The pharmacogenomics journal Vol. 18; no. 1; pp. 106 - 112 |
---|---|
Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.01.2018
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23 |
ISSN: | 1470-269X 1473-1150 |
DOI: | 10.1038/tpj.2016.67 |