Context: Dietary treatment of obesity could be improved if predictive information about the individual’s genetic response to diet was available. Adipose tissue has been the focus of efforts to identify candidate genes. Perilipin is a major protein found in adipocytes, and perilipin knockout mice are lean and resistant to diet-induced obesity.

Objective: The objective of the study was to examine the association of several polymorphisms at the perilipin (PLIN) locus with obesity and weight reduction in response to a low-energy diet in obese patients.

Design: This study was a 1-yr randomized (depending on the PLIN genotype) trial with three follow-up evaluations.

Setting: The study was conducted at a university research center.

Subjects: One hundred fifty obese patients (body mass index, 42 ± 8 kg/m²) at baseline and 48 patients who completed the dietary follow-up treatment for weight loss participated in the study.

Interventions: Subjects completed a 1-yr low-energy diet.

Main Outcomes Measurements: Body weight (BW) at baseline and 3, 6, and 12 months was measured.

Results: The minor A-allele at the PLIN 11482G>A polymorphism was associated with lower baseline BW. Moreover, we found a gene-diet interaction (P = 0.015) between this polymorphism and weight loss in patients that completed the 1-yr dietary treatment. Diet resulted in significant decreases in BW (from 114.3 ± 3.9 kg at baseline to 105.5 ± 3.5 kg at 1 yr; P lineal trend, 0.020) in GG patients (n = 33). Conversely, carriers of the minor A allele (n = 15) did not show significant changes in BW (from 105.0 ± 4.6 kg at baseline to 104.3 ± 4.4 kg at 1 yr; P lineal trend, 0.985). This gene-diet interaction remained statistically significant, even after adjustment for differences in BW at baseline and for other potential confounders.

Conclusions: PLIN11482A carriers were resistant to weight loss, suggesting that this polymorphism may predict outcome of BW reduction strategies based on low-energy diets.