title: Atenolol induced HDL-C change in the pharmacogenomic evaluation of antihypertensive responses (PEAR) study.
abstract: 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.
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, Florida, United States of America.
authors.forename: Caitrin W
authors.initials: CW
authors.lastname: McDonough
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Gillis
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alsultan
authors.forename: Shin-Wen
authors.initials: SW
authors.lastname: Chang
authors.forename: Marina
authors.initials: M
authors.lastname: Kawaguchi-Suzuki
authors.forename: Jason E
authors.initials: JE
authors.lastname: Lang
authors.forename: Mohamed Hossam A
authors.initials: MH
authors.lastname: Shahin
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Buford
authors.forename: Nihal M
authors.initials: NM
authors.lastname: El Rouby
authors.forename: Ana C C
authors.initials: AC
authors.lastname: Sá
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: John G
authors.initials: JG
authors.lastname: Gums
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001262:Atenolol / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D016014:Linear Models; D008049:Lipase / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D044465:White People / Q000235:genetics; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000959:Antihypertensive Agents; D001262:Atenolol; D008076:Cholesterol, HDL; D047628:Estrogen Receptor alpha; D008049:Lipase; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008565:Membrane Proteins; D017350:N-Acetylgalactosaminyltransferases; D011506:Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C513055:ABCB1 protein, human; C506487:ESR1 protein, human; C504173:LIPC protein, human; C555482:LRP5 protein, human; C471300:STARD3NL protein, human; C526492:FTO protein, human