TY - JOUR

T1 - No consistent effect of ADRB2 haplotypes on obesity, hypertension and quantitative traits of body fatness and blood pressure among 6,514 adult Danes

AU - Gjesing, Anette P

AU - Sparsø, Thomas

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Olsen, Niels V

N1 - Keywords: Adult; Blood Pressure; Body Mass Index; Case-Control Studies; Denmark; Female; Genetic Variation; Genotype; Haplotypes; Humans; Hypertension; Male; Middle Aged; Obesity; Quantitative Trait Loci; Receptors, Adrenergic, beta-2 Export Date: 4 November 2009Source: ScopusArt. No.: e7206

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Evidence regarding the association of variation within ADRB2, the gene encoding the beta-adrenergic receptor 2 (ADRB2) with obesity and hypertension is exceedingly ambiguous. Despite negative reports, functional impacts of individual genetic variants have been reported. Also, functional haplotypes as well as haplotype combinations affecting expression levels in vivo of ADRB2 mRNA and protein as well as receptor sensitivity have been reported. The aim of the present study was therefore to evaluate if variations within ADRB2 as haplotypes or as haplotype combinations confer an increased prevalence of obesity and hypertension among adults. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped five variants required to capture common variation in a region including the ADRB2 locus in a population-based study of 6,514 unrelated, middle-aged Danes. Phases of the genotypes were estimated in silico. The variations were then investigated for their combined association with obesity, hypertension and related quantitative traits. The present study did not find consistent evidence for an association of ADRB2 variants with either obesity or hypertension when variations were analysed in a case-control study. The same lack of impact was also seen in the quantitative trait analyses, apart from nominal differences on waist-to-hip ratio and systolic blood pressure between specific haplotype combinations. CONCLUSIONS/SIGNIFICANCE: In a population-based sample of 6,514 Danes we found no consistent associations between five common variants which tag the ADRB2 locus and prevalence of obesity or hypertension neither when analysed as individual haplotypes nor as haplotype pairs.

AB - BACKGROUND: Evidence regarding the association of variation within ADRB2, the gene encoding the beta-adrenergic receptor 2 (ADRB2) with obesity and hypertension is exceedingly ambiguous. Despite negative reports, functional impacts of individual genetic variants have been reported. Also, functional haplotypes as well as haplotype combinations affecting expression levels in vivo of ADRB2 mRNA and protein as well as receptor sensitivity have been reported. The aim of the present study was therefore to evaluate if variations within ADRB2 as haplotypes or as haplotype combinations confer an increased prevalence of obesity and hypertension among adults. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped five variants required to capture common variation in a region including the ADRB2 locus in a population-based study of 6,514 unrelated, middle-aged Danes. Phases of the genotypes were estimated in silico. The variations were then investigated for their combined association with obesity, hypertension and related quantitative traits. The present study did not find consistent evidence for an association of ADRB2 variants with either obesity or hypertension when variations were analysed in a case-control study. The same lack of impact was also seen in the quantitative trait analyses, apart from nominal differences on waist-to-hip ratio and systolic blood pressure between specific haplotype combinations. CONCLUSIONS/SIGNIFICANCE: In a population-based sample of 6,514 Danes we found no consistent associations between five common variants which tag the ADRB2 locus and prevalence of obesity or hypertension neither when analysed as individual haplotypes nor as haplotype pairs.

U2 - 10.1371/journal.pone.0007206

DO - 10.1371/journal.pone.0007206

M3 - Journal article

C2 - 19779622

VL - 4

SP - e7206

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 9

ER -