15 343

Cited 0 times in

고지혈증을 보이는 인슐린비의존성 당뇨병 환자에서의 Apolipoprotein E 다형성

Other Titles
 Apolipoprotein E polymorphism in non-insulin-dependent diabetes mellitus patients with hyperlipdemia 
Authors
 김정호 
Department
 Dept. of Laboratory Medicine (진단검사의학교실) 
Issue Date
1995
Description
의학과/박사
Abstract
[한글] Apolipoprotein E(이하 Apo E로 약함)는 저비중지단백 (Low density lipoprotein, LDL) 수용체와 간 Apo E 수용체의 ligand로서 작용하여 지단백대사에 중요한 역할을 하는 것으로 알려져 있다. Apo E 단백은 다형성을 보이는 유전자에 의해 생성되며 E2, E3, 및 E4의 세 대립 표현형을 보이게 된다. 각 개인은 부모로부터 각 1종씩의 Apo E 유전자를 물려 받으므로 E2/2, 2/3, 2/4, 3/3, 3/4, 및 4/4등 6종의 표현형을 갖게 된다. 당뇨병에서 고중성지방혈증을 보이는 기전의 하나로 Apo E 다형성과의 연관성이 제기된 바 있다. 본 연구에서는 인슐린비의존성 당뇨병 환자 80명과 정상대조군 40명의 Apo E 유전자형과 표현형을 검사하고 혈청 중성지방치와 콜레스테롤치와의 연관성을 살펴 보았다. Apo E 유전자형 분석은 DNA 증폭 후 HhaI 제한효소 절편다형성 분석법으로 검사하였다. Apo E 표현형검사는 neuraminidase로 처리한 혈청을 mini-vertical slab gel을 이용하여 등전위초점 전기영동을 한 후 웨스턴블롯을 하고 anti-human Apo E 항체를 이용하여 검출하는 방법을 이용하였다. 당뇨병 환자 80명에서 유전자형과 표현형검사의 일치율은 96.3%였고 정상군 40명을 포함한 총 120명에서의 일치율은 97.5% 였다. Apo E 유전자형과 표현형 검사가 일치된 117명의 Apo E 유전자형 빈도는 ε3/3, 68.4%; ε3/4, 16.2%; ε2/3, 12.8%; ε2/4, 1.7%; ε4/4, 0.9%; ε2/2, 0%였고 정상대조군과 인슐린비의존성 당뇨병군간에 의의있는 차이는 없었다(χ**2 =5.865, p=0.210). 또한 Apo E 대립인자 빈도는 각각 ε2, 0.073; ε3, 0.829; ε4, 0.098였고 역시 두 군간에 의의 있는 차이를 발견할 수 없었다(χ**2 =4.98, p=0.083). 한편 당뇨병 환자 중 정상중성지방혈증군 35명의 Apo E 유전자형별 비율은 ε3/3, 80.0%; ε3/4, 17.1%; ε2/3, 2.9%; ε 2/4, 0%; ε4/4, 0%: ε2/2, 0%였고 대립인자별 비율은 ε2, 0.014; ε3, 0.900; ε4, 0.086였으며, 42명의 고중성지방혈증군의 각 유전자형별 비율은 ε3/3, 66.7%: ε3/4, 16.7%: ε2/3, 11.9%: ε2/4, 2.4%; ε4/4, 2.4%: ε2/2, 0%였고 대립인자별 비율은 ε2, 0.071; ε3, 0.810; ε4, 0.119였다. 또한 인슐린비의존성 당뇨병군에서 고중성지방혈증군과 정상중성지방혈증군과의 Apo E 유전자형 빈도는 의의 있는 차이가 없었다(χ**2 =4.14, p=0.387). 또한 각각의 대립인자 비율에 있어서도 의의있는 차이를 발견할 수 없었다(ε2, p=0.093; ε3, p=0.089; ε4, p=0.345). 13명의 고콜레스테롤혈중 환자의 각 유전자형별 비율은 ε3/3, 61.5%; ε3/4, 30.8%; ε2/3, 7.7%; ε2/4, 0%: ε4/4, 0%: ε2/2, 0%였고 각 대립인자별 비율은 ε2, 0.038; ε3, 0.808; ε4, 0.154였으며, 64명의 정상콜레스테롤혈증군의 유전자형 및 대립인자별 비율은 ε3/3, 75.0%; ε3/4, 14.1%; ε2/3, 7.8%; ε2/4, 1.6%; ε4/4, 1.6%: ε2/2, 0%와 ε2, 0.047; ε3, 0.859: ε4=0.093였다. 고콜레스테롤혈증군과 정상콜레스테롤혈중군간에 Apo E 각 유전자형의 빈도는 의의있는 차이가 없었다(χ**2 =2.462, p=0.652). 또한 각각의 대립인자 비율에 있어서도 의의있는 차이를 발견할 수 없었다(ε2, p=0.664; ε3, p=0.211; ε4, p=0.273). 그리고 Apo ε2/3 및 Apo ε2/4와 같이 Apo ε2가 포함된 유전자형을 가진 사람 17명의 총콜레스테롤치 및 중성지방치의 평균 및 표준편차는 각각 173.1±36.3mg/dL와 138.4±85.9mg/dL였고 Apo ε3/3, Apo ε3/4, 및 Apo ε4/4와 같이 Apo ε2가 포함되지 않은 사람 100명의 총콜레스테롤치 및 중성지방치는 각각 195.0±45.6mg/dL와 166.3±107.4mg/dL 였으며, 총콜레스테롤치는 Apo ε2를 포함한 군에서 낮았고(p=0.022, Mann-Whitney U 검정), 중성지방치는 의미있는 차이가 없었다. 한편 본 연구에서의 Apo E 유전자형 빈도는 뉴질랜드인을 제외하고 타 민족의 것과 의의있는 차이가 없었다. 이상의 결과로 한국인 인슐린비의존성 당뇨병 환자의 경우 Apo E 다형성과 고지혈증 사이의 상호 연관성은 없는 것으로 사료되며 고중성지방혈증을 일으키는 기전으로 최저비중지단백(Very low density lipoprotein)의 생성 증가 또는 lipoprotein lipase의 활성 감소등 다른 요인이 관련된 것으로 사료되었다.
[영문] Apolipoprotein E(Apo E) has been known to have an important function for lipoprotein metabolism as a low denstiy lipoprotein receptor or hepatic apo E receptor. Apo E has three isoforms, E2, E3, and E4, produced by structural genes. Each individual should show one of six phenotypes, E2/2, E2/3, E2/4, E3/3, E3/4, or E4/4. Apo E polymorhphism was suggested to be associated with hypertriglyceridemia in diabetes mellitus. The aim of this study is to analyze the effect of Apo E polymorphism on hypertriglyceridemia or hypercholesterolemia in eighty diabetes mellitus patients and forty healthy controls. Apo E genotyping was determined with restriction isotyping by gene amplification and cleavage with HhaI restriction endonuclease. Apo E phenotyping was determined with mini-vertical slab gel isoelectric focusing of neuraminidase-treated sera, followed by immunoblotting using groat antihuman Apo E antibody. The genotypes and phenotypes of Apo E were concordant in seventy-seven patients among eighty diabetes mellitus patients(Concordant rate, 96.3%). Concordant rate among 120 subjects including healthy controls was 97.5%. Three discordant cases between Apo E genotype and phenotype were excluded for this study. APo E genotype frequencies for all 117 subjects with concordant genotyping and phenotyping were as follows, 68.4% for ε3/3, 16.2% for ε3/4, 12.8% for ε2/3, 1.7% for ε2/4, 0.9% for ε4/4, 0% for ε2/2. And we found no statistically significant difference of genotype frequencies between diabetes mellitus patients and healthy control group (χ**2= 5.865, p=0.210). Apo E allele frequencies were as follows; 0.073 for ε2, 0.829 for ε3, and 0.098 for ε4. There was no significant difference of allele frequencies between two groups (χ**2 =4.98, p=0.083). Apo E genotype frequencies of 35 diabetes mellitus patients with normotriglyceridemia were as follows; 80.0% for ε3/3; 17.1% for ε3/4, 2.9% for ε2/3, and 0% for ε2/4, ε4/4 or ε2/2. Allele frequencies of the same group were as follows; 0.014 for ε2, 0.90 for ε3, and 0.086 for ε4. Apo E genotype frequencies of 42 diabetes mellitus patients with hypertriglyceridemia were as follows, 66.7% for ε3/3, 16.7% for ε3/4, 11.9% for ε2/3, 2.4% for ε2/4, 2.4% for ε4/4, and 0% for ε2/2. Allele frequencies were as follows; 0.071 for ε2, 0.810 for ε3, and 0.119 for ε4. We found no significant difference of genotype frequncies between hypertriglyceridemia and normotriglyceridemia groups(χ**2 =4.14, p= 0.387). We found no significant difference of allele frequencies between hypertriglyceridemia and normotriglyceridemia groups with Fisher's exact tests (p= 0.093 for ε2, p=0.089 for ε3, p=0.345 for ε4). Apo E genotype frequencies of 13 diabetes mellitus patients with hypercholesterolemia were as follows; 61.5% for ε3/3, 30.8% for ε3/4, 7.7% for ε2/3, and 0% for ε2/4, ε4/4 or ε2/2. And allele frequencies of the same group were as follows; 0.038 for ε2, 0.808 for ε3, and 0.154 for ε4. There was no statistically significant difference of genotype(χ**2 =2.462, p=0.652) and allele frequencies(ε2, p=0.664; ε3, p=0.211; ε4, p=0.273, Fisher's exact test) between hypercholesterolemia and normocholesterolemia(n=64) groups. The means and standard deviations of serum total cholesterol and triglyceride levels in Apo ε2/3 or Apo ε2/4 subjects(n=17) were 173.1±36.3 mg/dL and 138.4±85.9 mg/dL, respectively. And serum total cholesterol and triglyceride levels in Apo ε3/3, Apo ε3/4, or Apo ε4/4 subjects(n=100) were 195.0±45.6 mg/dL and 166.3±107.4 mg/dL, respectively. Total cholesterol levels were significantly decreased among subjects who had Apo ε2(p=0.022, Mann-Whitney U-Wilcoxon rank sum W test), but we found no significant difference of serum triglyceride levels between two groups. Apo E allele frequencies of our 117 cases were not significantly different from those in Japanese(n=576, χ**2 =5.2, p=0.074), except genotype frequencies of Apo ε2/3, 12.8% for our study and 6.1% for Japanese(Fisher's exact test, p=0.023). We found no significant difference of Apo E allele frequencies of our subjects comparing with the other Koreans(n=152, χ**2 =0.933, p=0.627), Mexican-American(n=964, χ**2 =2.596, p=0.273) or Caucasian(n=3033, χ**2 =5.05, p=0.08), except with New Zealander(n=426, χ**2 = 9.7, p=0.0078). In conclusion, the observations indicated that there was no association between Apo E genotype and hypertriglyceridemia or hypercholesterolemia in diabetes mellitus patients, and other mechanisms, such as increased production of very low density lipoprotein or decreased activity of lipoprotein lipase may play a more improtant role.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000004249
Files in This Item:
제한공개 원문입니다.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 3. Dissertation
Yonsei Authors
Kim, Jeong Ho(김정호) ORCID logo https://orcid.org/0000-0003-2479-0548
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/117735
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links