Abstract 4437: Genome-Wide Association Study for the Response to Antihypertensive Medication: HOMED-BP-GENE Study

Abstract

AAntihypertensive therapy is a powerful approach to prevent the cardiovascular disease. However, the responsiveness of the therapy is highly individual due to the variability of genetic or environmental factors. To elucidate the genetic background underlying antihypertensive drug responsiveness, we carried out a genome-wide association study (GWAS). The subjects studied were recruited from the participants of HOMED-BP study (UMIN Registered ID C000000137, http://www.cpt.med.tohoku.ac.jp/HOMED-BP/) after obtaining the informed consent for the genetic analysis. After DNA extraction from peripheral blood, about half million single nucleotide polymorphisms (SNPs) were examined using GeneChip Genome-Wide Human SNP5.0 Array (Affymetrix). Home blood pressure (HBP) was measured every day within 1 hour after wake-up and before going to bed using HEM747-IC-N (Omron). The study protocol was approved by the ethical committee of Osaka University. SNP5.0 Array analysis was demonstrated for 300 participants. Antihypertensive therapy for 4weeks decreased their average HBP from 149.9/88.8mmHg to 137.7/82.2mmHg in early morning and 142.6/82.3mmHg to 129.1/74.7mmHg before going to bed. We excluded the SNPs data that showed low call rate, lack of Hardy-Weinberg’s equilibrium and minor allele frequency less than 0.05. Eight SNPs were significantly (p<0.001) associated with mean HBP reduction both in the early morning and at bedtime. Nine SNPs were more significantly (p<0.0001) associated with morning HBP reduction and 3 SNPs were associated with bedtime HBP reduction. In conclusion, GWAS of antihypertensive medication revealed several candidate loci responsible for a month therapy with the difference between morning and evening.