The beta(2)-adrenergic receptor Arg16-gly polymorphism and interactions involving beta(2)- and beta(3)-adrenergic receptor polymorphisms are associated with variations in longitudinal serum lipid profiles: the Bogalusa Heart Study.

TitleThe beta(2)-adrenergic receptor Arg16-gly polymorphism and interactions involving beta(2)- and beta(3)-adrenergic receptor polymorphisms are associated with variations in longitudinal serum lipid profiles: the Bogalusa Heart Study.
Publication TypeJournal Article
Year of Publication2004
AuthorsD Hallman, M, Srinivasan, SR, Chen, W, Boerwinkle, E, Berenson, GS
JournalMetabolism
Volume53
Issue9
Pagination1184-91
Date Published2004 Sep
ISSN0026-0495
KeywordsAfrican Continental Ancestry Group, Age Factors, Algorithms, Amino Acid Substitution, Body Mass Index, Cardiovascular Diseases, Child, Cholesterol, LDL, DNA Primers, European Continental Ancestry Group, Female, Genotype, Humans, Lipids, Longitudinal Studies, Male, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Receptors, Adrenergic, beta-3, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, Sex Factors, Triglycerides
Abstract

We examined the effects of combined genotypes of the beta(2)-adrenergic receptor (AR) Arg(16)-Gly and beta(3)-AR Trp(64)-Arg polymorphisms on longitudinal serum total (T-C) and low-density lipoprotein cholesterol (LDL-C) profiles in 1,198 subjects examined multiple times (6,488 observations) from 1973 to 1996 in the Bogalusa Heart Study, at ages from 4.5 to 38 years. Within 5-year age groups, T-C was significantly (P <.05) higher in beta(2)-AR Arg(16)/Arg(16) homozygotes than in Gly(16) carriers among those 4 to 8 (171.4 +/- 30.0 v 161.5 +/- 27.7 mg/dL), 9 to 13 (167.7 +/- 28.6 v 162.4 +/- 27.4 mg/dL), and 14 to 18 (158.8 +/- 29.6 v 154.7 +/- 27.5 mg/dL) years of age, but not in those 19 to 23, 24 to 28, 29 to 33, or 34 to 38 years of age. The beta(3)-AR polymorphism was not associated with variation in either T-C or LDL-C. In multilevel polynomial growth curve models, the combination of the beta(2)-AR Arg(16)/Arg(16) genotype with either the beta(3)-AR Arg(64)/Arg(64) or Trp(64)/Arg(64) genotypes, denoted AA/AX, was associated with variation in longitudinal T-C (P <.01) and LDL-C (P <.01) profiles. The association between combined beta(2)/beta(3)-AR genotype and lipid profiles differed among race/sex groups, being most marked in black females, in whom the AA/AX combination was associated with higher T-C and LDL-C profiles across all ages. In White males, the AA/AX combination was most strongly associated with higher lipids in adults. In black males and white females, lipid profiles differed little between genotype groups. Our findings suggest that the beta(2)-AR Arg(16)-Gly genotype influences T-C and LDL-C levels in an age-specific manner, that it may interact with beta(3)-AR Trp(64)-Arg genotypes to influence longitudinal T-C and LDL-C profiles, and that the effect of combined beta(2)/beta(3)-AR genotypes on T-C and LDL-C profiles may differ among race/sex groups.

Alternate JournalMetab. Clin. Exp.
PubMed ID15334382
Grant ListDK47487-06A2 / DK / NIDDK NIH HHS / United States
DK58026 / DK / NIDDK NIH HHS / United States
EY12386-02 / EY / NEI NIH HHS / United States
GM56515 / GM / NIGMS NIH HHS / United States
HL38844 / HL / NHLBI NIH HHS / United States
HL51021 / HL / NHLBI NIH HHS / United States
HL54457 / HL / NHLBI NIH HHS / United States
HL54464 / HL / NHLBI NIH HHS / United States
HL54481 / HL / NHLBI NIH HHS / United States
HL70568 / HL / NHLBI NIH HHS / United States