title: Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women.
abstract: Perilipin coats intracellular lipid droplets and modulates adipocyte lipolysis. We have evaluated the association between several polymorphisms at the perilipin (PLIN) locus (PLIN1 : 6209T > C, PLIN4 : 11482G > A, PLIN5 : 13041A > G, and PLIN6 : 14995A > T) with obesity-related phenotypes in 1589 White subjects randomly selected from a general Spanish population. In women (n = 801), the less common alleles of PLIN1 and PLIN4, in strong linkage disequilibrium (D' : 0.96), were significantly associated with lower body mass index. Carriers of the allele 2 (6209C) at the PLIN1 locus weighed significantly less (-2.2 kg; p = 0.007) than women homozygotes for the wild-type genotype. The same was true for 11482A carriers at PLIN4 (p = 0.01). Moreover, the PLIN4 variant was associated with significantly lower waist-to-hip ratio, plasma glucose, and triacylglycerol concentrations. No significant associations with these obesity-related phenotypes were found in men. In agreement with these results, statistically significant gene-gender interactions were obtained when the risk of obesity was estimated (281 subjects were obese and 1308 non-obese). Only in women, PLIN1 and PLIN4 variant alleles (6209C and 11482A) were associated with a lower obesity risk [Odds ratio (OR) = 0.58, 95% confidence interval (CI): 0.38-0.93 and OR = 0.56, 95% CI: 0.36-0.89, respectively]. In summary, our data suggest that common alleles at the PLIN locus modulate body weight and metabolic variables in humans.
authors.affiliation: The Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: L
authors.initials: L
authors.lastname: Qi
authors.forename: D
authors.initials: D
authors.lastname: Corella
authors.forename: J V
authors.initials: JV
authors.lastname: Sorlí
authors.forename: O
authors.initials: O
authors.lastname: Portolés
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: O
authors.initials: O
authors.lastname: Coltell
authors.forename: D
authors.initials: D
authors.lastname: Godoy
authors.forename: A S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015992:Body Mass Index; D001835:Body Weight; D002352:Carrier Proteins; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D000070778:Perilipin-1; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D044465:White People
chemical_list: D002352:Carrier Proteins; C000602978:PLIN1 protein, human; D000070778:Perilipin-1; D010750:Phosphoproteins