Association of β2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels

Antonio Petrone, Sara Zavarella, Gianluca Iacobellis, Simona Zampetti, Andrea Vania, Sergio Di Pietro, Andrea Galgani, Frida Leonetti, Umberto Di Mario, Raffaella Buzzetti

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The β2 adrenergic receptor (β2-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between β2-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the β2-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5′LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the β2 -AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5′LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5′LC-Arg19 homozygous (P = 0.03 and P = 0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P = 0.02 and P = 0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P = 0.01 and P = 0.03, respectively). The 5′LC-Cys19 Arg16Gln27 haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5′LC-Arg19Gly16Glu27 haplotype (P = 0.05 and P = 0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5′LC-Cys19Arg16Gln27 haplotype.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalEuropean Journal of Human Genetics
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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LDL Cholesterol
Adrenergic Receptors
Haplotypes
Triglycerides
Genotype
Obesity
Lipid Mobilization
Genes
Genetic Predisposition to Disease
Glycogen
Genetic Promoter Regions
Energy Metabolism
Single Nucleotide Polymorphism
Linear Models
Regression Analysis
Phenotype
Lipids
Weights and Measures

Keywords

  • Adrenergic receptor β gene
  • Body mass index
  • Haplotype
  • LDL-cholesterol
  • Obesity
  • Triglycerides

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Association of β2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels. / Petrone, Antonio; Zavarella, Sara; Iacobellis, Gianluca; Zampetti, Simona; Vania, Andrea; Di Pietro, Sergio; Galgani, Andrea; Leonetti, Frida; Di Mario, Umberto; Buzzetti, Raffaella.

In: European Journal of Human Genetics, Vol. 14, No. 1, 01.01.2006, p. 94-100.

Research output: Contribution to journalArticle

Petrone, A, Zavarella, S, Iacobellis, G, Zampetti, S, Vania, A, Di Pietro, S, Galgani, A, Leonetti, F, Di Mario, U & Buzzetti, R 2006, 'Association of β2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels', European Journal of Human Genetics, vol. 14, no. 1, pp. 94-100. https://doi.org/10.1038/sj.ejhg.5201521
Petrone, Antonio ; Zavarella, Sara ; Iacobellis, Gianluca ; Zampetti, Simona ; Vania, Andrea ; Di Pietro, Sergio ; Galgani, Andrea ; Leonetti, Frida ; Di Mario, Umberto ; Buzzetti, Raffaella. / Association of β2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels. In: European Journal of Human Genetics. 2006 ; Vol. 14, No. 1. pp. 94-100.
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abstract = "Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The β2 adrenergic receptor (β2-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between β2-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the β2-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5′LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the β2 -AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5′LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5′LC-Arg19 homozygous (P = 0.03 and P = 0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P = 0.02 and P = 0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P = 0.01 and P = 0.03, respectively). The 5′LC-Cys19 Arg16Gln27 haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5′LC-Arg19Gly16Glu27 haplotype (P = 0.05 and P = 0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5′LC-Cys19Arg16Gln27 haplotype.",
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AU - Di Pietro, Sergio

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