The association of CREBRF variant rs373863828 with body composition in adult Samoans

Objective: The minor allele of rs373863828, a missense variant in CREBRF, is associated with higher BMI but lower odds of type 2 diabetes in Pacific Islanders. Methods: To test if this protective effect operates through metabolically favorable body fat distribution, we examined the association of the minor A allele with body composition, measured using dual-energy x-ray absorptiometry (DXA), in a cross-sectional study of n=421 Samoan adults. Results: We replicated our earlier finding that this allele was associated with higher weight and BMI, although it was statistically significant only in women. There was no significant association of genotype with percent body fat, visceral adiposity or fat distribution, although in women, the A allele was associated with greater total fat mass (p=0.02), android (p=0.009) and trunk fat (p=0.01). In both sexes, age- and height-adjusted average lean mass was significantly greater per copy of the A allele: 2.16 kg/copy in women and 1.73 kg/copy in men. Conclusions: These data do not support a primary role of fat distribution in mediating the association between rs373863828 genotype and type 2 diabetes risk. We suggest an alternative hypothesis: those with the A allele may more efficiently regulate blood glucose because of their greater absolute lean mass.