本論文的目的在探討第二、三型高脂血症患者的遺傳變異，並對相關的apoE、apoB基因進行多型性分析。在30位高脂血症的基因突變分析上，利用聚合酵素鏈反應(PCR)技術，放大apoE、apoB基因上和受體結合的部分片段，再以單股核酸構形多型性(SSCP)及DNA定序法來檢測患者的遺傳變異。結果發現3位HLP II患者的FDB:R3500W。由於此突變產生一限制酵素NlaIII的切割點，以此特性對一FDB患者95-020家族進行R3500W檢測，結果發現其父親及兩位弟妹亦帶有此突變。
在apoE基因的多型性分析上，由隨機抽樣的93位正常人及上述30位高脂血症患者的血液樣品中抽取基因組DNA，放大包含apoE基因表現子4的多型性片段，再以限制酵素HhaI之限制片段長度多型性(RFLP)，檢測各樣品的多型性，結果發現高脂血症族群均已對偶基因頻率(13.3%)較正常人族群(8.6%)為高，ε4對偶基因頻率(3.3%)則較正常人族群(8.6%)為低。
在50位正常人族群的apoB基因多型性分析上，以PCR放大包含Signal peptide、AluI、XbaI、MaeI、MspI、EcoRI、3'HVR等多型性的DNA片段，再以RFLP或膠體電泳檢測各樣品的多型性，結果得到各多型性的對偶基因頻率及異型合子率，除了MaeI多型性外，皆符合哈溫定律。對其二個對偶基因的多型性而言，其中signal peptide、AluI、MaeI多型性的三種基因型皆被檢測到，XbaI及EcoRI多型性只檢測到二種基因型，MspI則未檢測到任何多型性變化，3'HVR多型性檢測到6種對偶基因及13種基因型的變化。同一樣品的各多型性對偶基因，並無明顯的連鎖現象。

The aims of this study were to examine the genetic variation of the patients with HLPIII or HLPII and to analyse the polymorphisms of apo E and apo B genes. Genomic DNA extracted from 30 hyperlipidemic subjects was used to amplify fragment containing receptor binding domain of apoE and apoB genes. The PCR amplified products were subjected to single strand conformation polymorphism (SSCP) analysis. PCR products with aberrant SSCP bands were cloned and DNA sequencing was done to study their molecular lesions. Three heterozygotes with FDB3500W were identified. The mutation creates a new NlaIII site and can be used to examine the family members of the affected individual. The results reveal that the proband 95-020 inherited the mutation from his father. Among four siblings examined, two of them carry the mutation.
To analyse polymorphism of the apoE gene, genomic DNA extracted from randomly sampled 93 normal individuals and 30 hyperlipidemic subjects was used to amplify exon 4 fragment containing polymorphic site. The PCR amplified products were analysed by HhaI restriction fragment length polymorphism (RFLP).
In the hyperlipidemic subjects, the frequency of ε2 allele was higher than that of the normal population (13.3% vs 8.6%); on the other hand, lower frequency of ε4 allele was found (3.3% vs 8.6%). In the analysis of apoB gene polymorphism, genomic DNA from 50 normal individuals was used to amplified fragments containing polymorphic sites : signal peptide (exon 1), AluI (exon 14), XbaI, MaeI, MspI(exon 26), EcoRI(exon 29), and 3'HVR. The PCR amplified products were analysed by RFLP or gel electrophoresis. The allele frequency and heterozygosity were computed and chi-square tested for Hardy-Weinberg equilibrium. Five polymorphic sites examined are in Hardy-Weinberg equilibrium except MaeI polymorphism. For diallelic polymorphisms, three genotypes were observed for signal piptide, AluI, and MaeI polymorphisms; on the other hand, only one genotype was found for MspI polymorphism. For 3'HVR, six alleles and thirteen genotypes were observed. Little linkage disequilibrium was observed between alleles of 7 polymorphisms examined.