title: Melatonin Pathway and Atenolol-Related Glucose Dysregulation: Is There a Correlation?
abstract: Lower melatonin level, melatonin receptor gene variations, and atenolol treatment are associated with glucose dysregulation. We investigated whether atenolol-related glucose and melatonin changes are correlated, and whether single nucleotide polymorphisms (SNPs) in melatonin candidate genes contribute to interindividual variation in glucose change. Hypertensive Caucasians (n = 232) from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study treated with atenolol for 9 weeks were studied. Urinary 6-sulfatoxymelatonin (aMT6s) was measured pre- and posttreatment and normalized to urinary creatinine. Pharmacogenetic effects on glucose change of 160 SNPs in 16 melatonin candidate genes were assessed with multiple linear regression. Atenolol was associated with increased glucose (1.8 ± 10.1mg/dl, P = 0.02) and decreased aMT6s (-4.5 ± 10.1 ng/mg, P < 0.0001). However, the aMT6s change was not correlated with post-atenolol glucose change. SNP rs11649514 in PRKCB was associated with glucose change (P = 1.0×10(-4)). PRKCB is involved in the melatonin-insulin regulatory pathway, and may be important in mediating clinically meaningful atenolol-related hyperglycemia.
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center of Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Chang
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center of Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center of Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: McDonough
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center of Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
authors.forename: T Y
authors.initials: TY
authors.lastname: Langaee
authors.affiliation: Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
authors.forename: N
authors.initials: N
authors.lastname: Nasiri Kenari
authors.affiliation: Division of Endocrinology, Diabetes & Nutrition, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Beitelshees
authors.affiliation: Department of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Gums
authors.affiliation: Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Chapman
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Turner
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center of Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.|Division of Cardiology, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center of Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.|Division of Cardiology, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Cooper-DeHoff
mesh_terms: D001262:Atenolol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D064546:Protein Kinase C beta / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D044465:White People
chemical_list: D001786:Blood Glucose; C054513:6-sulfatoxymelatonin; D001262:Atenolol; D064546:Protein Kinase C beta; D005947:Glucose; D008550:Melatonin