β2肾上腺素能受体基因多态性及相关单倍型与甘油三酯和低密度脂蛋白胆固醇水平的关联

Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels.

作者信息

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

机构信息

Endocrinology, Department of Clinical Sciences, University La Sapienza, Rome, Italy.

出版信息

Eur J Hum Genet. 2006 Jan;14(1):94-100. doi: 10.1038/sj.ejhg.5201521.

DOI:10.1038/sj.ejhg.5201521

PMID:16251889

Abstract

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.

摘要

肾上腺素能受体调节脂质动员、能量消耗和糖原分解。β₂肾上腺素能受体（β₂-AR）基因可能是一个潜在的候选基因，可用于解释人类肥胖及相关性状的部分遗传易感性。关于β₂-AR基因多态性与肥胖相关代谢紊乱之间的关联，已发表的报告结果相互矛盾。我们在一组超重/肥胖受试者中研究了β₂-AR的三种多态性及相关单倍型在肥胖及相关性状中的作用。我们对642名连续招募的超重/肥胖受试者的β₂-AR启动子区域的一个单核苷酸多态性（SNP）（5'LC-Cys19Arg）和编码区域的两个SNP（Gly16Arg和Gln27Glu）进行了特征分析，并对这些受试者进行了广泛的临床和生化分析。使用多元线性回归分析研究多态性对定量变量的影响。与5'LC-Arg19纯合子相比，5'LC-Cys19纯合子的甘油三酯和低密度脂蛋白胆固醇水平更高（分别为P = 0.03和P = 0.01）。与Gly16Arg多态性的Gly/Gly基因型相比，Arg/Arg基因型的甘油三酯和低密度脂蛋白胆固醇水平也有类似升高（分别为P = 0.02和P = 0.01）；与Gln27Glu多态性的Glu/Glu基因型相比，Gln/Gln基因型的甘油三酯和低密度脂蛋白胆固醇水平也有类似升高（分别为P = 0.01和P = 0.03）。与5'LC-Arg(19)Gly(16)Glu(27)单倍型相比，5'LC-Cys(19)Arg(16)Gln(27)单倍型导致甘油三酯和低密度脂蛋白胆固醇水平显著升高（分别为P = 0.05和P = 0.02）。我们的研究结果为先前关于这三种基因变异对脂质表型影响的观察提供了更多证据；特别是携带5'LC-Cys(19)Arg(16)Gln(27)单倍型的超重/肥胖受试者中甘油三酯和低密度脂蛋白胆固醇水平的升高。