Genetics of abdominal visceral fat levels

The purpose of this review is to explore the evidence accumulated thus far that suggests a genetic component to the observed variation in abdominal visceral fat (AVF) levels. The precise determination of AVF levels in humans is limited to methods such as computerized tomography and magnetic resonance imaging; thus, few studies have examined the role of genetic factors on this phenotype. Evidence from the Québec Family Study (QFS) and the HERITAGE Family Study indicates that between 50-55% of the variance in AVF levels, adjusted for total fatness, is attributable to genetic factors. Additionally, a major gene hypothesis for AVF was supported in the both the QFS and HERITAGE Family Study. However, after adjustment for total fat mass the support for a major gene was reduced, suggesting that a major gene which affects fat mass may also affect AVF either directly (pleiotropy), or indirectly. The search for candidate genes that may impact AVF levels is in its infancy, and few candidate genes have been identified. However, the glucocorticoid receptor (GRL), ss3 adrenergic receptor (ADRB3), and fatty acid binding protein 2 (FABP2) genes have been significantly associated with AVF or intra-abdominal fat levels in humans. In addition, three quantitative trait loci obtained from crosses of mice, the Do2, Mob4, and Qbw1 loci have been linked with mesenteric or abdominal fat and are thus considered positional candidate genes for AVF levels. The search for candidate genes or random genetic markers associated with AVF levels is a challenging prospect. However, given the significant heritability of this phenotype, the quest remains promising. Am. J. Hum. Biol. 11:225-235, 1999. Copyright 1999 Wiley-Liss, Inc.