A Study On The Mutations In Exon 5～9 Of LPL Gene

Lipoprotein lipase(LPL) is a critical enzyme of catabolic metabolism in lipoproteins, its major function is the hydrolysis of the core triglycerides of circulating chylomicrons and very low density lipoproteins. The deficiency of LPL enzyme activities can cause hypertriglyceridemia, which is often the result of gene mutations, but the Ser447 -* stop mutation is commonly considered to be an advantageous mutation, which may decrease plasma TG level and increase plasma HDLc level respectively. To investigate the distribution of gene mutations in LPL and to study the relationship between LPL mutations and plasma lipid, the LPL gene(exon5~9 including intron-exon boundaries) was examined by PCR-SSCP analysis, and the amplified products showing abnormal pattern on SSCP were sequenced using dideoxy-mediated chain-termination. One missense mutation was found in 48 hypertriglyceridemic patients and identified to be Pro207-Leu by sequencing, pedigree analysis of this proband has been carried out and showed that the proband's father is also a carrier of this mutation. In addition the nonsense mutation Ser447-stop was screened by PCR-SSCP and identified by PCR-RFLP, 12 heterozygous mutations were found in 48 hypertriglyceridemic patients, and 1 homozygous and 38 heterozygous mutations were found in 121 control people. The frequency of Ser447-stop in hypertriglyceridemic group is lower than that in control group by chi-square test. No mutation can be found in exon 6~8 of LPL. This study will provide some information on the species and distributions of LPL gene mutations in Chinese population. These basic data may be beneficial to diagnosis and therapy of hypertriglyceridemia and related diseases.