Song Weihua, Yu Hui, Lin Yahui, Sun Kai, Zhang Yinhui, Song Yan, Hui Rutai, Chen Jingzhou
Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China.
Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China.
Biochem Biophys Res Commun. 2015 Jan 24;456(4):896-900. doi: 10.1016/j.bbrc.2014.12.053. Epub 2014 Dec 18.
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.
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.
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.
The functional PLIN1 rs6496589 may influence the risk of central obesity through possible regulation of lipid storage.
perilipin覆盖脂肪细胞和类固醇生成细胞中的脂滴。其主要作用是调节脂肪细胞内的脂解作用。我们的目的是研究PLIN1基因常见变异与中国非相关成年人中心性肥胖之间的关联。
对869例中心性肥胖患者和869例年龄及性别匹配的非中心性肥胖个体进行病例对照研究。通过聚合酶链反应（PCR）和限制性酶切分析对两个PLIN1变异（rs6496589和rs8179078）进行基因分型。此外，在一个由629例中心性肥胖患者和518例对照组成的独立人群中重复该变异与中心性肥胖的关联研究。最后，评估rs6496589与THP-1衍生巨噬细胞中脂质积累增强之间的关系。
患者组中PLIN1 rs6496589等位基因频率以及CG+GG基因型频率远低于对照组。使用多元逻辑回归分析对传统危险因素进行校正后，rs6496589G等位基因频率与中心性肥胖风险显著降低相关（比值比0.71，95%置信区间：0.59 - 0.86，P = 0.001）。这些结果在一项独立研究中得到证实。未发现PLIN1 rs8179078与中心性肥胖之间存在关联。此外，体外试验显示，与非携带者相比，纯合rs6496589G等位基因在THP-1衍生巨噬细胞中的脂滴积累较低。
功能性PLIN1 rs6496589可能通过对脂质储存的潜在调节影响中心性肥胖风险。
