Lipoprotein lipase gene polymorphism rs1059611 functionally influences serum lipid concentrations

Area of Science:

• Genetics
• Biochemistry
• Cardiovascular Disease Research

Background:

• Single nucleotide polymorphisms (SNPs) in the lipoprotein lipase (LPL) gene are frequently associated with variations in lipid concentrations.
• Understanding these genetic associations is crucial for comprehending lipid metabolism and cardiovascular risk.

Purpose of the Study:

• To validate the association between the LPL gene SNP rs1059611 and serum lipid concentrations in the Chinese Han population.
• To investigate the potential biological mechanisms underlying this association.

Main Methods:

• Genotyping of 5664 participants for the rs1059611 SNP.
• Quantification of LPL gene expression (mRNA and protein) using real-time PCR and western blotting.
• Functional analysis using luciferase reporter assays and electrophoretic mobility-shift assays (EMSA).

Main Results:

• Significant associations were found between rs1059611 and increased HDL-C (P = 5.65 × 10⁻⁵) and decreased TG concentrations (P = 2.68 × 10⁻⁷).
• The C allele of rs1059611 correlated with higher LPL mRNA and protein expression levels.
• Luciferase assays indicated allele-specific differences in transcriptional activity, and EMSA revealed differential transcription factor binding.

Conclusions:

• The LPL gene variant rs1059611 is significantly associated with HDL-C and TG levels in the Chinese Han population.
• This SNP may exert its effect through differential binding of transcription factors, influencing LPL gene transcription.