Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels.
Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-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 beta(2)-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 beta(2)-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 beta(2)-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-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) 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-Cys(19)Arg(16)Gln(27) haplotype.
Petrone
Antonio
A
Endocrinology, Department of Clinical Sciences, University La Sapienza, Rome, Italy.
Zavarella
Sara
S
Iacobellis
Gianluca
G
Zampetti
Simona
S
Vania
Andrea
A
Di Pietro
Sergio
S
Galgani
Andrea
A
Leonetti
Frida
F
Di Mario
Umberto
U
Buzzetti
Raffaella
R
D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000235:genetics; D050177:Overweight / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
D008078:Cholesterol, LDL; D018343:Receptors, Adrenergic, beta-2; D014280:Triglycerides