Objective: 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.
Methods: 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).
Results: 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.
Conclusion: 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.
Keywords: 3′-UTR; 3′-untranslation region; BMI; DBP; EMSA; Expression; GLU; GWAS; Genome-Wide Association Study; HDL-C; HWE; Hardy–Weinberg equilibrium; LD; LDL-C; Lipid; Lipoprotein lipase; MAF; SBP; SNP; TG; Transcription factor; body mass index; diastolic blood pressure; electrophoretic mobility-shift assay; glucose; high-density lipoprotein cholesterol; linkage disequilibrium; low-density lipoprotein cholesterol; minor allele frequency; single nucleotide polymorphism; systolic blood pressure; triglycerides.
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