Angiotensin-converting Enzyme Gene Polymorphism and Cerebrovascular Disease in Korean population

한국인의 ACE(Angiotensin-converting Enzyme) 유전자의 다형성과 뇌혈관 질환과의 관계에 대한 연구

  • Lee Jin Woo (Department of Physiology, College of Oriental Medicine, Kyunghee University) ;
  • Lee Kyung Jin (Department of Internal Medicine, College of Oriental Medicine, Kyunghee University) ;
  • Rho Sam Woong (Department of Physiology, College of Oriental Medicine, Kyunghee University) ;
  • Kim Jae Jong (Genotech Co.) ;
  • Bae Hyung Sup (Department of Internal Medicine, College of Oriental Medicine, Kyunghee University) ;
  • Hong Moo Chang (Department of Physiology, College of Oriental Medicine, Kyunghee University) ;
  • Shin Min Kyu (Department of Physiology, College of Oriental Medicine, Kyunghee University) ;
  • Kim Young Suk (Department of Internal Medicine, College of Oriental Medicine, Kyunghee University) ;
  • Bae Hyun Su (Department of Physiology, College of Oriental Medicine, Kyunghee University)
  • 이진우 (경희대학교 한의과대학 생리학교실) ;
  • 이경진 (경희대학교 한의과대학 심계내과학교실) ;
  • 노삼웅 (경희대학교 한의과대학 생리학교실) ;
  • 김재중 ;
  • 배형섭 (경희대학교 한의과대학 심계내과학교실) ;
  • 홍무창 (경희대학교 한의과대학 생리학교실) ;
  • 신민규 (경희대학교 한의과대학 생리학교실) ;
  • 김영석 (경희대학교 한의과대학 심계내과학교실) ;
  • 배현수 (경희대학교 한의과대학 생리학교실)
  • Published : 2002.08.01

Abstract

Angiotensin-converting enzyme (ACE) gene polymorphism, which consists of presence (insertion, I) or absence (deletion, D) of a 250-bp fragment, is associated with ischemic heart disease, renovascular disease, systemic lupus erythematosus. Subjects with the DD genotype have higher levels of circulating ACE than subjects with the II genotype and show an increased tendency towards vascular wall thickness and contribute to the development of vascular disease. But the association between I/D polymorphism of the ACE gene and cerebrovascular disease is still controversial. The aim of this study was to determine whether the DNA polymorphism of the ACE are associated with cerebrovascular disease in Korean population. The study group comprised 377 Korean patients admitted to Kyunghee Oriental Medical Center in the year of 2000 for the treatment of brain infarction or brain hemorrhage. Magnetic resonance imaging(MRI) was performed for each patient to determine the stroke phenotype, infarction or hemorrhage. The 183 subjects without evidence of brain infarction or brain hemorrhage were selected from the some ethnical population(control group). Venous blood samples were drawn from each subject for the extraction of DNA. Genotypes of ACE were determined by polymerase chain reaction amplification of the genomic DNA. Case and control genotype frequencies were compared by chi-square testing. Both the patients and the controls were classified respectively into 4 groups: age less than forty years, age forty one to fifty, age fifty one to sixty, age greater than sixty years. There were no significant differences in the distributions of ACE genotypes among the patients with infarction, with hemorrhage and controls (Infarction: D/D 15.8%, I/D 46.7%, I/I 37.5%, Hemorrhage: D/D 15.1%, I/D 46.5%, I/I 38.4%, Control: D/D 18.6%, I/D 50.3%, I/I 31.2%). There was a significant difference in the distribution of ACE genotypes between the age greater than sixty year subgroup of patient with brain hemorrhage and the control (Hemorrhage: D/D 0%, I/D 55.6%, I/I 44.4%, Control: D/D 13.0%, I/D 63.0%, I/I 23.9%; Pearson Chi-Square value 5.956, P<0.05). Furthermore, the frequency of the ACE D/D type declined with increasing age both in the patient and control group (Patient group: age < 50 D/D 21.5%, age > 50 D/D 14.42%; Control group: age < 50 D/D 21.0%, age > 50 D/D 14.2%). In conclusion there is no clear association between ACE polymorphism and cerebrovascular disease in Korean population. Although, there was a tendency for the frequency of the ACE D/D type declined with increasing age in both patients and controls.

Keywords

References

  1. 임상중풍학 김영석
  2. Am J Hum Genet. v.51 Evidence from combined segregation and linkage analysis, that a variant of the angiotensis I-converting enzyme(ACE) gene controls plasma ACE levels. Tiret L;Rigat B;Visvikis S;Breda C;Corvol P;Cambien F;Soubrier F
  3. Stroke v.26 no.8 Angiotensin-converting enzyme gene deletion polymorphism. A new risk factor for lacunar stroke but not carotid atheroma Markus HS;Barley J;Lunt R;Bland JM;Jeffery S;Carter ND;Brown MM.
  4. J Hypertens v.13 no.12 Lack of association between angiotensin converting enzyme gene insertion/deletion polymorphism and stroke Ueda S;Weir CJ;Inglis GC;Murray GD;Muir KW;Lees KR.
  5. J Hum Hypertens. v.8 no.8 Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin 1-converting enzyme Sharma P;Carter ND;Barley J;Brown MM.
  6. J Formos Med Assoc. v.99 no.12 Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese Lin JJ;Yueh KC;Lin GY;Chang DC;Chang CY;Shieh HL;Harn HJ.
  7. Nucleic Acids Research v.19 no.19 A rapid non- enzymatic method for the preparation of HMW DNA from blood for RFLP studies Debomoy K.Lahiri;John I.Nurnberger, Jr.
  8. Nature v.15 no.359 Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Cambien F;Poirier O;Lecerf L;Evans A;Cambou JP;Arveiler D;Luc G;Bard JM;Bara L;Ricard S;Tiret L;Amouyel P;Alhenc-Gelas F;Soubrier F
  9. Circulation v.90 no.2 level and gene polymorphism of angiotensin- converting enzyme in relation to myocardial infarction. Cambien F;Costerousse O;Tiret L;Poirier O;Lecerf L;Gonzales MF;Evans A;Arveiler D;Cambou JP;Luc G;Rakotovao R;Ducimetiere P;Soubrier F;Alhenc-Gelas F.,
  10. N Engl J Med. v.18;315 no.12 Risk of stroke in male cigarette smokers Abbott RD;Yin Y;Reed DM;Yano K.
  11. 노인병 v.2 no.1 한국인에서 ACE와 ApoE 유전자다형성의 분포 및 혈중지질에 미치는 영향 최윤호;이원로
  12. Stroke v.26 no.8 Angiotensin-converting enzyme gene deletion polymorphism, A new risk factor for lacunar stroke but not carotid atheroma Markus HS;Barley J;Lunt R;Bland JM;Jeffery S;Carter ND;Brown MM.
  13. J Hypertens v.13 no.12 Lack of association between angiotensin converting enzyme gene insertion/deletion polymorphism and stroke Ueda S;Weir CJ;Inglis GC;Murray GD;Muir KW;Lees KR.
  14. J Hum Hypertens. v.8 no.8 Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin 1-converting enzyme Sharma P;Carter ND;Barley J;Brown MM.
  15. J Formos Med Assoc. v.99 no.12 Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese Lin JJ;Yueh KC;Lin GY;Chang DC;Chang CY;Shieh HL;Harn HJ.
  16. J Clin Invest. v.94 no.3 Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals. Morris BJ;Zee RY;Schrader AP.
  17. Atherosclerosis v.132 no.2 Polymorphism of the angiotensin-converting enzyme (ACE) gene in patients with thrombotic brain infarction Doi Y;Yoshinari M;Yoshizumi H;Ibayashi S;Wakisaka M;Fujishima M.