Obese subjects carrying the 11482G>A polymorphism at the perilipin locus are resistant to weight loss after dietary energy restriction.
BACKGROUND
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.


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


METHODS
The study was conducted at a university research center.


METHODS
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.


METHODS
Subjects completed a 1-yr low-energy diet.


METHODS
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.
Nutrition and Genomics Laboratory, Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, Massachusetts 02111, USA.
Dolores
D
Corella
Lu
L
Qi
José V
JV
Sorlí
Diego
D
Godoy
Olga
O
Portolés
Oscar
O
Coltell
Andrew S
AS
Greenberg
José M
JM
Ordovas
D000225:Adenine; D000328:Adult; D000368:Aged; D000483:Alleles; D031204:Caloric Restriction; D002352:Carrier Proteins; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology; D005260:Female; D006147:Guanine; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000178:diet therapy* / Q000235:genetics*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D015431:Weight Loss / Q000235:genetics*
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D006147:Guanine; D000225:Adenine