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 receptor (GRL), lipoprotein lipase (LPL) and adrenergic receptor (ADR) gene markers contribute to individual differences in indicators of adiposity and abdominal 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 six skinfolds. Abdominal fat areas measured by computed tomography and adjusted for age, sex and total fat mass in all analyses. GRL BclI, alpha2A-ADR DraI and beta2-ADR BanI markers were typed by Southern blot, and other markers by polymerase chain reaction technique. RESULTS: It is confirmed that the 4.5 kb allele of the GRL BclI polymorphism 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. Furthermore, the alpha2-ADR DraI variant is associated with lower cross-sectional areas of abdominal total (P = 0.003) and subcutaneous (P = 0.012) adipose tissue. Gene-gene interactions between GRL and alpha2-ADR genes affecting overall 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 the three genes were considered together in the same analysis, significant interactions having influence on overall adiposity (P = 0.017), abdominal total (P = 0.032) and visceral fat (P = 0.002) were observed. About 1-2% of the total variation in total fatness and abdominal fat was explained by these gene-gene interactions. CONCLUSION: There is an association between the GRL BclI polymorphism and increased AVF levels independent of the level of total body fat. The alpha2-ADR DraI variant is associated with a lower cross-sectional area of abdominal 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 genetic architecture of body fat content and adipose tissue distribution is complex although some genes, like GRL, may have ubiquitous effects.