Interactions among the alpha 2-, beta 2-, and beta 3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study

The gene-gene interactions between markers in the alpha 2-, beta 2-, and be ta 3-adrenergic receptor (ADR) genes and obesity-related phenotypes were st udied in the Quebec Family Study (QFS) cohort. The prevalence of the Arg al lele of the Arg16Gly polymorphism in the beta 2-ADR gene was higher (49%) i n males with a body mass index (BMI) of 35 kg/m(2) or higher versus those w ith a BMI less than 35 kg/m(2) (33%; P = .010). The beta 2-ADR gene Arg16Gl y end Gln27Glu polymorphisms were associated with plasma total and low dens ity lipoprotein (LDL) cholesterol concentrations. In addition, the homozygo tes for the 6.3-kb allele of Dral polymorphism in the alpha 2-ADR gene had the lowest mean abdominal subcutaneous fat area (P = .012) and total fat ar ea (P = .003), as well as insulin area, under the curve during an oral gluc ose tolerance test ([OGTT] P = .004). Several ADR gene-gene interaction eff ects on abdominal fat distribution and plasma lipids were detected. First, significant interactions between alpha 2- and beta 3-ADR genes were observe d on total (P = .015) and subcutaneous (P = .004) abdominal fat. Second, in teraction effects between alpha 2- and beta 2-ADR gene variants influenced total, high-density lipoprotein (HDL), and LDL cholesterol concentrations. Finally, there were interactions between markers within the beta 2-ADR gene affecting plasma triglyceride concentrations and subcutaneous abdominal fa t. From these results, we conclude that polymorphisms in the ADR genes cont ribute to body fat and plasma lipid variability in men. Gene-gene interacti ons among the ADR genes contribute to the phenotypic variability in abdomin al obesity and plasma lipid and lipoprotein, but not in visceral fat levels . Copyright (C) 2000 by W.B. Saunders Company.