Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Quebec Family Study

OBJECTIVE: To investigate whether interactions between glucocorticoid recep tor (GRL), lipoprotein lipase (LPL) and adrenergic receptor (ADR) gene mark ers contribute to individual differences in indicators of adiposity and abd ominal obesity, including visceral fat level. DESIGN AND SUBJECTS: Cross-sectional study; 742 individuals from the phase 2 of the Quebec Family Study cohort. MEASUREMENTS: Total body fat assessed by hydrodensitometry and the sum of s ix skinfolds. Abdominal fat areas measured by computed tomography and adjus ted for age, sex and total fat mass in all analyses. GRL Bcl1, alpha ZA-ADR Dra1 and beta2-ADR Ban I markers were typed by Southern blot, and other ma rkers by polymerase chain reaction technique. RESULTS: It is confirmed that the 4.5 kb allele of the GRL Bcl1 polymorphis m is associated with a higher amount of abdominal visceral fat (AVF) depot (P for trend < 0.001) independent of the level of total body fat. Furthermo re, the alpha2-ADR Dra1 variant is associated with lower cross-sectional ar eas of abdominal total (P = 0.003) and subcutaneous (P = 0.012) adipose tis sue. Gene-gene interactions between GRL and alpha2-ADR genes affecting over all adiposity (P = 0.016) as well as between GRL and beta2-ADR genes (P = 0 .049) having influence on total abdominal fat levels were observed. When th e three genes were considered together in the same analysis, significant in teractions having influence on overall adiposity (P = 0.017), abdominal tot al (P = 0.032) and visceral fat (P = 0.002) were observed. About 1-2% of th e total variation in total fatness and abdominal fat was explained by these gene-gene Interactions. CONCLUSION: There is an association between the GRL Bcl1 polymorphism and i ncreased AVF levels independent of the level of total body fat. The alpha2- ADR Dra1 variant is associated with a lower cross-sectional area of abdomin al total fat. Numerous Interactions between GRL and ADR markers on overall adiposity and total abdominal fat as well as between GRL, LPL and ADR genes on overall adiposity, abdominal total and visceral fat suggest that the ge netic architecture of body fat content and adipose tissue distribution is c omplex although some genes, like GRL, may have ubiquitous effects.