Major gene for abdominal visceral fat area in the Québec Family Study

OBJECTIVES: The abdominal visceral fat depot is considered to be the most atherogenic, diabetogenic and hypertensiogenic fat depot of the human body. Although the amount of abdominal visceral fat is correlated with total body fat, there remain considerable inter-individual differences in visceral fat at any level of body fat content. No study has been reported to date on the contribution of genetic factors to the variability in abdominal visceral fat level. DESIGN: Abdominal visceral fat area was assessed by computerized tomography in 382 adult men and women from 100 families of the Québec Family Study. After adjustment for the effects of age and age plus total fat mass (assessed by underwater weighing), a major gene hypothesis for abdominal visceral fat area was investigated using segregation (POINTER) analyses. RESULTS: Segregation analysis of the age-adjusted variable indicated that variability in visceral fat area was accounted for by a major gene transmitted according to Mendelian expectations. Data support an autosomal recessive locus, associated with high levels of abdominal visceral fat, accounting for 51% of the phenotypic variance and affecting 10% of the sample. An additional 21% of the variance was due to multifactorial (polygenic and/or familial environment) sources. However, after adjusting for total fat mass, support for a major gene for abdominal visceral fat was less strong. CONCLUSIONS: These results suggest that the familial etiology of abdominal visceral fat level involves a major autosomal recessive locus. Given the critical role of abdominal visceral fat in the metabolic complications of obesity, it will now be important to identify the gene responsible for the high levels of abdominal visceral fat observed in some adults and to investigate whether this gene is the same as that which influences total body fat content.