Atenolol Induced HDL-C Change in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study

We sought to identify novel pharmacogenomic markers for HDL-C response to atenolol in participants with mild to moderate hypertension. We genotyped 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study on the Illumina HumanCVD Beadchip. During PEAR, participants were randomized to receive atenolol or hydrochlorothiazide. Blood pressure and cholesterol levels were evaluated at baseline and after treatment. This study focused on participants treated with atenolol monotherapy. Association with atenolol induced HDL-C change was evaluated in 232 whites and 152 African Americans using linear regression. No SNPs achieved a Bonferroni corrected P-value. However, we identified 13 regions with consistent association across whites and African Americans. The most interesting of these regions were seven with prior associations with HDL-C, other metabolic traits, or functional implications in the lipid pathway: GALNT2, FTO, ABCB1, LRP5, STARD3NL, ESR1, and LIPC. Examples are rs2144300 in GALNT2 in whites (P=2.29x10^-4, β=-1.85 mg/dL) and rs12595985 in FTO in African Americans (P=2.90x10^-4, β=4.52 mg/dL), both with consistent regional association (P<0.05) in the other race group. Additionally, baseline GALNT2 expression differed by rs2144300 genotype in whites (P=0.0279). In conclusion, we identified multiple gene regions associated with atenolol induced HDL-C change that were consistent across race groups, several with functional implications or prior associations with HDL-C.