Apolipoprotein E Polymorphism in Patients with Myocardial Infarction

BACKGROUND AND OBJECTIVES: In this study we investigated the association between the polymorphism of apolipoprotein E and the development of myocardial infarction, and assessed whether this polymorphism produces any changes of plasma lipid level. SUBJECTS AND METHODS: A total of 182 patients participated in this study and were divided into two groups; 91 patients with myocardial infarction (MI group) and 91 patients with no known heart disease (control group). For both groups we analyzed the clinical parameters, the changes of plasma lipid level and the degree of polymorphism of apolipoprotein E. RESULTS: Total cholesterol, triglyceride and LDL cholesterol levels were significantly higher in the MI group, while the HDL cholesterol level was significantly lower. Compared with the control group, the frequency of epsilon2 allele was significantly lower while that of epsilon3 allele was significantly higher in the MI group. As for the control group, the triglyceride level was significantly higher in the patients with epsilon 2 allele than in those without epsilon 2 allele, and the total cholesterol level was significantly higher in the patients with epsilon 4 allele than in those without epsilon 4 allele. In the MI group, the plasma lipid levels were not significantly different from those in the control group. CONCLUSION: We suggested that apolipoprotein E polymorphism could affect the lipid metabolism as well as the development of myocardial infarction. However further study is needed in patients with myocardial infarction.

Analysis of low - density - lipoprotein receptor gene in Korean patients with familial hypercholesterolemia / 대한내과학회지

Familial hypercholesterolemia (FH) is a common autosomal dominant disorder caused by a defect in the low-density-lipoprotein (LDL) receptor, disrupting the normal control of cholesterol metabolism. We have collected 86 FH families for over 5 years who met following Dx criteria 1) hypercholesterolemia over 280 mg/dl 2) Achilles tendon xanthoma thicker than 9 mm, and 3) familial tendency, and characterized the pattern of mutations in Korea FH patients. METHOD: Mutation was screened with linkage analysis into two ways; large structural rearrangements were screened by genomic Southern blotting or long-PCR technique, and small structural rearrangements were screened by PCR of each exon followed by SSCP analysis. The exact mutation sites were confirmed by sequencing. RESULT: 1) Large mutation: Three different large deletions(FH110, FH29, FH32) were found in 7(11.5%) among 61 families screened. FH110 was a deletion of 5.7kb from intron 8 to 12, which was found in 5 unrelated families. FH29 was a deletion of 3.8kb from intron 6 to 8, and FH32 was a deletion of 2kb from intron 6 to 7. These three deletions have not been reported previously. The mechanism of deletion was unequal crossover from mispairing Alu-sequences. 2) Small or point mutations: Nineteen different small mutations were found in 19(31.4%) among 86 families screened . These mutations comprised 9 missense, 3 nonsense, 2 splicing mutations, 3 small deletions, and 2 small insertions. One missense mutation (Pro664Leu) was found in 6 unrelated families. Among these mutations, 12 have not been reported previously. CONCLUSIONS: LDL receptor gene mutations are heterogeneous in Korean FH patients. We could not observe founder mutation but detect common mutations.

Korean multicenter clinical trial of simvastatin ( KS-1 study ) / 대한내과학회지

The aim of this study was to investigate the efficacy of simvastatin to improved lipid profiles in hypercholesterolemic Korean patients. METHODS: From 25 hospitals in Korea, 478 hypercholesterolemic patients were enrolled from November 1996 to April 1998. The inclusion criteria was hypercholesterolemia over 240 mg/dl after diet therapy for 1 month or hypercholesterolemia over 220 mg/dl in patients with definite evidence of ischemic heart disease. Simvastatin 10mg was started and doubled up to 40mg if total cholesterol level remained higher than 200 mg/dl at monthly check. Of 478 subjects, 344 patients in whom study protocol was not violated were analyzed. RESULTS: Male to female ratio was 27:73 and 47% of the subjects were in 6th decade. Hypertension, coronary artery disease, and diabetes mellitus were present in 30, 10, and 4% of the subjects. Baseline lipid profile (mean of total cholesterol-LDL-HDL-triglyceride mg/dl) was 274-185-52-188. The dose of simvastatin for 3 months was 10/10/10mg in 61% of subjects, 10/20/20mg in 21%, 10/10/20mg in 7%, and 10/20/40mg in 12%. The change of total cholesterol level(before-4wk-8wk-12wk-withdrawal 4wk) was 274-209- 205-198-250, and the maximal reduction rate was 27%. The change of LDL-cholesterol was 185-123-116-110-159, with maximal reduction rate 39%. The change of HDL-cholesterol was 52-54-56-55-54, with maximal increase rate 9%. The change of tryglyceride was 188-161- 164-162-189, with maximal reduction rate 15%. The value before/after treatment of ApoA1, ApoB, and Lp(a) was 129/129, 138/83, and 9.3/10.7, respectively. The level of LDL-cholesterol at the end of treatment was below 100mg/dl in 36% of subjects, 100-130 in 45%, 130-160 in 16%, and over 160mg/dl in 4%. The reduction rate of LDL-cholesterol was different between subjects whose LDL decreased below 100 and those whose LDL did not decrease below 130mg/dl, which suggests the existence of the individual difference of responsiveness to simvastatin. There were only 3 subjects (0.9%) who showed increase of liver enzyme over 3 times as the upper normal limit. Conclusion: Simvastatin is effective in improving lipid profiles in hypercholesterolemic Korean patients without serious side effects.

Analysis of low - density - lipoprotein receptor gene in Korean patients with familial hypercholesterolemia / 대한내과학회지

Familial hypercholesterolemia (FH) is a common autosomal dominant disorder caused by a defect in the low-density-lipoprotein (LDL) receptor, disrupting the normal control of cholesterol metabolism. We have collected 86 FH families for over 5 years who met following Dx criteria 1) hypercholesterolemia over 280 mg/dl 2) Achilles tendon xanthoma thicker than 9 mm, and 3) familial tendency, and characterized the pattern of mutations in Korea FH patients. METHOD: Mutation was screened with linkage analysis into two ways; large structural rearrangements were screened by genomic Southern blotting or long-PCR technique, and small structural rearrangements were screened by PCR of each exon followed by SSCP analysis. The exact mutation sites were confirmed by sequencing. RESULT: 1) Large mutation: Three different large deletions(FH110, FH29, FH32) were found in 7(11.5%) among 61 families screened. FH110 was a deletion of 5.7kb from intron 8 to 12, which was found in 5 unrelated families. FH29 was a deletion of 3.8kb from intron 6 to 8, and FH32 was a deletion of 2kb from intron 6 to 7. These three deletions have not been reported previously. The mechanism of deletion was unequal crossover from mispairing Alu-sequences. 2) Small or point mutations: Nineteen different small mutations were found in 19(31.4%) among 86 families screened . These mutations comprised 9 missense, 3 nonsense, 2 splicing mutations, 3 small deletions, and 2 small insertions. One missense mutation (Pro664Leu) was found in 6 unrelated families. Among these mutations, 12 have not been reported previously. CONCLUSIONS: LDL receptor gene mutations are heterogeneous in Korean FH patients. We could not observe founder mutation but detect common mutations.

Korean multicenter clinical trial of simvastatin ( KS-1 study ) / 대한내과학회지

The aim of this study was to investigate the efficacy of simvastatin to improved lipid profiles in hypercholesterolemic Korean patients. METHODS: From 25 hospitals in Korea, 478 hypercholesterolemic patients were enrolled from November 1996 to April 1998. The inclusion criteria was hypercholesterolemia over 240 mg/dl after diet therapy for 1 month or hypercholesterolemia over 220 mg/dl in patients with definite evidence of ischemic heart disease. Simvastatin 10mg was started and doubled up to 40mg if total cholesterol level remained higher than 200 mg/dl at monthly check. Of 478 subjects, 344 patients in whom study protocol was not violated were analyzed. RESULTS: Male to female ratio was 27:73 and 47% of the subjects were in 6th decade. Hypertension, coronary artery disease, and diabetes mellitus were present in 30, 10, and 4% of the subjects. Baseline lipid profile (mean of total cholesterol-LDL-HDL-triglyceride mg/dl) was 274-185-52-188. The dose of simvastatin for 3 months was 10/10/10mg in 61% of subjects, 10/20/20mg in 21%, 10/10/20mg in 7%, and 10/20/40mg in 12%. The change of total cholesterol level(before-4wk-8wk-12wk-withdrawal 4wk) was 274-209- 205-198-250, and the maximal reduction rate was 27%. The change of LDL-cholesterol was 185-123-116-110-159, with maximal reduction rate 39%. The change of HDL-cholesterol was 52-54-56-55-54, with maximal increase rate 9%. The change of tryglyceride was 188-161- 164-162-189, with maximal reduction rate 15%. The value before/after treatment of ApoA1, ApoB, and Lp(a) was 129/129, 138/83, and 9.3/10.7, respectively. The level of LDL-cholesterol at the end of treatment was below 100mg/dl in 36% of subjects, 100-130 in 45%, 130-160 in 16%, and over 160mg/dl in 4%. The reduction rate of LDL-cholesterol was different between subjects whose LDL decreased below 100 and those whose LDL did not decrease below 130mg/dl, which suggests the existence of the individual difference of responsiveness to simvastatin. There were only 3 subjects (0.9%) who showed increase of liver enzyme over 3 times as the upper normal limit. Conclusion: Simvastatin is effective in improving lipid profiles in hypercholesterolemic Korean patients without serious side effects.