A Preliminary Study Of LPL Gene Abnormalities In Patients With Hyperlipidemia

Objective:Lipoprotein lipase is one of the key enzymes in lipid metabolism. The defect of LpL gene is often associated with endogenous hypertriglyceridemia and coronary heart disease. Exon4 of LPL gene codes for the domain that contains amino acid residues identified as the catalysis active site. Once mutation occurs in the exon4, LPL function may be lost or decreased seriously, and the degradation of CM and VLDL will be damaged. In this paper, we screened for the mutation appearing in the exon4 and its flanking sequences in patients with hyperlipidemia, and discussed its effect on the pre-mRNA secondary structure.Method:Genomic DNA was extracted from leucocyte of patients with primary hyperlipidemia. A segment of DNA including exon4 of LPL gene was analyzed by PCR-SSCP. The PCR product with abnormal SSCP pattern was cloned and sequenced. Secondary structure of Pre-mRNA segment is predicted by computer software.Results:1)A C T transition mutation at ? of intron3 was found in a Chinese withhyperlipidemia.2)There are conformational differences in the secondary structure between mutantand normal pre-mRNA segment analysed.Conclusion:There is a pedigree with CT transition mutation at ? of intron3 of LPL gene among Chinese group. This mutation has a certain effect on the pre-mRNA secondary structure, and thus may have influence on pre-mRNA splicing, LPL gene expressing and LPL activities. Therefore, this mutation may be one of risk factors of hypertriglyceridaemia.