Association Of The Lipoprotein Lipase Gene S447X And HindⅢ Polymorphisms With Serum Lipids And Coronary Heart Disease

[Objective] To investigate the relationship between lipoprotein lipase gene S447X and HindIII polymorphisms with serum lipids and coronary heart disease.[Methods] We addressed this issue in a case-control study in which 249 subjects with angiographically documented coronary artery disease and 167 subjects without CHD ( excluded by coronarography). Automated Biochemical Analyzer was used to measure the concentration of serum TC. TG. HDL-C. LDL-C, VLDL-C and ApoB.The sLDL level was detected by polyacrylamid gel. PCR-RFLP and PCR-SSCP were used to detect S447X and Hindlll polymorphisms in lipoprotein lipase gene.[Results] (1) Between the CHD patients and controls the levels of serum TCMG. LDL-C. sLDL, VLDL-C. ApoB were significant higher and HDL-C level was significant lower in the former than those in the latter (p<0.05 or 0.01). ^Through binary logistic regression analysis LDL-C. sLDL. gender (male). advanced age were confirmed to be risk factors for CHD and high level of HDL-C was a protective factor for CHD.Partial correlation analysis shows that the severity of coronary artery stenosis is positively related to the levels of serum LDL-C. sLDL and negatively to the HDL-C level(rLD;-C=0.290, P<0.001; rsldl=0.404, P<0.001; rJDL-C=-0.139 , P<0.01).Mutivariate linear regression demonstrated that sLDL percentage was most closely contributive to predicting the severity of the coronaryartery stenosis. (3) The LPL gene .HindIII polymorphism in intron8 was due to a T-G transversion . S447X polymorphism in exon9 was due to a CG transversion which creates a premature termination codon and result in a truncated LPL molecule lacking C-terminal dipeptide Ser-Gly.No significant difference was found in the frequencies of genotypes and alleles of the two polymorphisms between controls and CHD patients (P>0.05) and the two polymorphisms were not improved to be risk factors for CHD. (4) H- allete of Hindlll site showed good influences on serum lipids,but not significant(P>0.05)except VLDL-C (P0.05). X allete of S447X site also made good effects on serum lipids, leading to the lower concentration of serum TG. LDL-C. VLDL-C . ApoB (P<0.05)and higher concentration of HDL-C (P<0.01),especially when the concentration of serum TG<1.7mmo/l. Althrough there were no significant difference in the frequencies of genotypes and alleles between male and'female subjects,the female subjects carrying the SX/XX genotypes showed significantly lower levels of TG(P<0.05), VLDL-C(P<0.01), sLDL(PO.Ol) and higher level of HDL-C (PO.05) compared with those carrying the SS genotype. No significant difference was found in male sugjects(P>0.05).[Conclusion] (l)The high levels of serum LDL-C . sLDL and gender(male)N advanced age were risk factors for CHD and high level of HDL-C was a protective factor for CHD. The severity of coronary artery stenosis is positively related to the levels of serum LDL-C. sLDL and negatively to the HDL-C level. (2)LPL gene Hindllland S447X polymorphisms were not risk factors for CHD and no significant difference was found in the frequencies of S447X and Hindlll genotypes and alleles between controls and CHD patients. (3)The X allele of LPL S447X polymorphism may have good effects on the profiles of serum lipids, especially reducing the concentration of serum TG. sLDL and increasing the concentration of HDL-C by increasing the catalytic activity of LPL. The good influence on serum lipids of X allete in female subjects were more obvious than that in male subjects.LPL SX/XX genotypes could be viewed as protective genotypefor CHD.