State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
Atherosclerosis. 2013 Aug;229(2):511-6. doi: 10.1016/j.atherosclerosis.2013.05.005. Epub 2013 May 18.
Dozens of single nucleotide polymorphisms (SNPs) in the lipoprotein lipase (LPL) gene have been reported to be associated with lipid concentrations. The aim of this study was to validate the association between rs1059611 in the LPL gene and serum lipid concentrations in the Chinese Han population and explore the biological relevance.
A total of 5664 participants were recruited and genotyped for the SNP. Gene expression levels of LPL in blood cells were evaluated by real-time PCR and western blotting analysis. The functional potential of the SNP was examined by luciferase reporter assay and electrophoretic mobility-shift assay (EMSA).
We observed significant associations between rs1059611 and increased HDL-C (P = 5.65 × 10(-5)) and decreased TG concentrations (P = 2.68 × 10(-7)). We also found that participants with the C allele had higher mRNA expression level (P = 0.0334) and protein expression level (P = 0.0641) of LPL. The luciferase activity of the rs1059611 T construct was 0.69-fold of the rs1059611 C construct (P = 0.0009). The EMSA showed that the binding of the transcription factor(s) differed for the alleles of the SNP.
The results of our study demonstrated that rs1059611 was associated with HDL-C and TG concentrations in Chinese Han population and might have a functional effect on the transcription of LPL by differential binding of transcription factors.
脂蛋白脂肪酶（LPL）基因中的数十个单核苷酸多态性（SNP）已被报道与脂质浓度相关。本研究旨在验证 LPL 基因中 rs1059611 与中国汉族人群血清脂质浓度的关联，并探讨其生物学相关性。
共招募了 5664 名参与者进行 SNP 基因分型。通过实时 PCR 和 Western blot 分析评估血细胞中 LPL 的基因表达水平。通过荧光素酶报告基因检测和电泳迁移率变动分析（EMSA）检测 SNP 的功能潜力。
我们观察到 rs1059611 与 HDL-C 升高（P = 5.65×10(-5)）和 TG 浓度降低（P = 2.68×10(-7)）显著相关。我们还发现，携带 C 等位基因的参与者具有更高的 LPL mRNA 表达水平（P = 0.0334）和蛋白表达水平（P = 0.0641）。rs1059611 T 构建体的荧光素酶活性是 rs1059611 C 构建体的 0.69 倍（P = 0.0009）。EMSA 表明，该 SNP 等位基因的转录因子结合存在差异。
我们的研究结果表明，rs1059611 与中国汉族人群的 HDL-C 和 TG 浓度相关，并且可能通过转录因子的差异结合对 LPL 的转录具有功能影响。
