Interactions among the glucocorticoid receptor, lipoprotein lipase, and adrenergic receptor genes and plasma insulin and lipid levels in the Quebec family study

The aim of the study was to investigate the possible interactions among the glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic re ceptor (ADR) genes on plasma insulin and lipid levels. The study was cross- sectional and based on 742 individuals from phase 2 of the Quebec Family St udy (QFS) cohort. Gene markers were identified by Southern blot analysis or polymerase chain reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral glucose tolerance test (OGTT) were determined and insulin and glucose areas were computed. Triglyceride (TG) and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymati cally. The results show that GRL and LPL variants had independent effects o n plasma high-density lipoprotein cholesterol (HDL-C) and two beta2-ADR var iants were related to total cholesterol concentrations. The alpha2-ADR gene DraI polymorphism was the only variant that had an independent effect on t he plasma insulin area. Gene-gene interaction effects were found between GR L and alpha2-ADR genes for low-density lipoprotein cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P = .045). Higher-order int eraction effects involving GRL, LPL, and ADR markers were observed for the plasma insulin area (P = .001 to .025) but not the glucose area. After corr ection for multiple tests, the findings remained essentially unchanged for the insulin area but became nonsignificant for the lipid phenotypes, In con clusion, multiple interactions among GRL, LPL, and ADR gene markers contrib ute to insulin metabolism and perhaps to lipid levels, while no significant effect is found for each gene separately. The LPL locus appears to determi ne the pattern of interactions with ADR and GRL loci. These results suggest that gene-gene interaction effects could play a role in the etiology of ri sk factors for common chronic diseases. Copyright (C) 2001 by W.B. Saunders Company.