肝脂酶基因启动子多态性与连锁不平衡分析

Analysis of hepatic lipase gene polymorphism and linkage disequilibrium

目的:探讨肝脂酶(hepatic lipase,HL)基因启动子-250G/A、-514C/T、-710T/C和-763A/G4个位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)的分布特征及连锁不平衡关系。方法:应用聚合酶链反应-限制性内切酶片段长度多态性技术,对112名三酰甘油(triglyceride,TG)正常者、103例高三酰甘油血症(hypertriglyceri-demics,HTG)患者的HL基因型和等位基因的分布频率进行分析,运用群体数理遗传学方法分析HL启动子4个基因位点SNP的遗传平衡吻合度及相互间连锁不平衡关系。结果:在HTG组中,-250A和-514T的等位基因频率及基因型频率均显著大于TG正常组(P<0.05);-710T/C位点仅有基因型频率在两组中有显著性差异(P<0.05),而等位基因频率无显著性差异(P>0.05);-763A/G位点的基因型频率及等位基因频率在两组中则均无差异(P>0.05)。4个SNP相互间均呈强连锁不平衡。对启动子区3个SNP位点两两组合的单倍体型频率分析表明,在HTG和TG正常者中也存在显著差异(P<0.05)。在单倍体型分析中,HTG者增加最显著的是HL-250A/-514T/-710C单倍体型。结论:HL启动子的3个SNP及单倍体型与HTG间存在显著相关性,本研究提供了HL基因启动子多态性的群体遗传学资料。

Objective To investigate the distribution characters and linkage disequilibrium of hepatic lipase gene-250G/A,-514C/T,-710T/C and-763A/G polymorphism.Methods The hepatic lipase（HL） gene polymorphism of 113 healthy controls and 102 patients with hypertriglyceridemics（HTG） were analyzed by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） .The four HL single nucleotide polymorphisms（SNPs） ,Hardy-Weinberg equilibrium and linkage disequilibrium were analyzed with population genetics methods.Results The frequencies of allele A at position-250 and allele T at position-514 significantly increased in HTG cases comparing with the healthy controls,so were their genotype frequencies.The frequencies of allele C at position-710 had no statistically significant differences between HTG cases and healthy controls,but its genotype were significant differences.Position-763 had no statistically significant differences in genotype and allele frequencies.Strong linkage disequilibrium was found among these SNP.Significant differences in the overall distribution of haplotype frequencies based on 3 and 2 SNP markers were found between two groups,with the most significant increase in the frequency of HL-250A/-514T/-710C haplotype based on 3 SNP markers in HTG patients.Conclusion The HTG is highly associated with-250A/-514T/-710C SNP.Moreover,our study has provided population genetics data on four HL promoter genes.