The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites

Food intake and weight gain are influenced by endocannabinoids whose actions are regulated by the fatty acid amide hydrolase (FAAH) enzyme. The homozygous Thr/Thr genotype of the functional Pro129Thr variant (rs324420) in the gene encoding FAAH was recently reported to associate with overweight and obesity in white and black populations. We investigated the Pro129Thr variant in relation to overweight and obesity in a relatively large population-based study sample of Danish whites (n=5,801). In case-control studies of obesity, a borderline association with the major Pro allele was identified; however, after correction for multiple testing, no association was found. Furthermore, a possible association between the major Pro allele and obesity was not supported by studies of obesity-related quantitative traits. In conclusion, in a large study sample, we were unable to find robust evidence of an association of the Pro129Thr FAAH variant with overweight, obesity, and any related quantitative traits among the examined whites.