β-AR polymorphisms and glycemic and lipid parameters in hypertensive individuals receiving carvedilol or metoprolol.
BACKGROUND
β-Blocker therapy and β-adrenergic receptor (β-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common β1 and β2-AR single-nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with β-blocker treatment assignment to affect these parameters.


METHODS
This was a post hoc analysis of a double-blinded clinical trial of nondiabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3 months, and after 6 months. Genotypes for β1-AR SNPs Ser49Gly & Gly389Arg and β2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed models were used to examine associations between β-AR polymorphisms, metabolic parameters, and SNP interactions with β-blocker therapy (p(interaction)).


RESULTS
The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol and 9.9% on carvedilol (P = 0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with β-blockade compared to the Glu27Glu genotype (P = 0.006). Both Arg16Gly (P = 0.012) and Gln27Glu (P = 0.037) SNPs were associated with higher triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (p(int) = 0.048).


CONCLUSIONS
These data suggest that insulin and triglycerides may be influenced by β2-AR polymorphisms in patients taking β blockers.
University of Wisconsin School of Pharmacy, Madison, WI, USA. ovardeny@pharmacy.wisc.edu
Orly
O
Vardeny
Gabriel
G
Nicholas
Alina
A
Andrei
Kevin A
KA
Buhr
Matt P
MP
Hermanson
John J
JJ
Moran
Michelle A
MA
Detry
James H
JH
Stein
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011412:Propanolamines / Q000627:therapeutic use*; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics; D014280:Triglycerides / Q000097:blood*
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002227:Carbazoles; D007328:Insulin; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D014280:Triglycerides; D000077261:Carvedilol; D008790:Metoprolol