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
KeywordsAge Factors, Algorithms, Amino Acid Substitution, Blacks, Body Mass Index, Cardiovascular Diseases, Child, Cholesterol, LDL, DNA Primers, 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, Whites
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.

DOI10.1016/j.metabol.2004.03.019
Alternate JournalMetabolism
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