A functional variant in the exon 5 of PLIN1 reduces risk of central obesity by possible regulation of lipid storage.

Purpose: Perilipin coats lipid droplets in adipocytes and steroidogenic cells. Its major role is in the regulation of intracellular lipolysis in adipocytes. Our aim was to examine the association between common variants at the PLIN1 gene and central obesity in unrelated Chinese adults.
Methods: A case-control study was carried out on 869 patients with central obesity and 869 age- and gender-matched individuals without central obesity. Two PLIN1 variants (rs6496589 and rs8179078) were genotyped by PCR and restriction enzyme analysis. In addition, the association of the variant with central obesity was replicated in an independent population of 629 central obesity patients and 518 controls. Finally, the relationship between rs6496589 and enhancing lipid accumulation in THP-1-derived macrophages was assessed.
Results: PLIN1 rs6496589 allele frequencies and genotype frequencies of CG+GG in the patients' group were much lower than those in the control group. After adjustment for conventional risk factors using multiple logistical regression analysis, rs6496589G allele frequencies were significantly associated with a lower risk of central obesity (OR 0.71, 95% CI: 0.59-0.86, P=0.001). These results were confirmed in an independent study. No association was found between PLIN1 rs8179078 and central obesity. Furthermore, in vitro assays revealed that homozygous rs6496589G alleles presented lower lipid droplet accumulation in THP-1-derived macrophages, compared with non-carriers.
Conclusions: The functional PLIN1 rs6496589 may influence the risk of central obesity through possible regulation of lipid storage.
(Copyright © 2014 Elsevier Inc. All rights reserved.)