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Angiotensin converting enzyme gene polymorphism and traditional Sasang classification in Koreans with cerebral infarction

2003; BioMed Central; Volume: 138; Issue: 3 Linguagem: Inglês

10.1034/j.1601-5223.2003.01605.x

1601-5223

Hyun‐Na Koo, Jong‐Cheon Joo, Kyung-Yo Kim, Nyeon‐Hyoung An, K.M. Lee, Hyung‐Min Kim,

Healthcare and Venom Research

HereditasVolume 138, Issue 3 p. 166-171 Open Access Angiotensin converting enzyme gene polymorphism and traditional Sasang classification in Koreans with cerebral infarction JAE-YOUNG UM, JAE-YOUNG UM Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Jeonbuk, Republic of KoreaSearch for more papers by this authorJONG-CHEON JOO, JONG-CHEON JOO Wonkwang University Hospital, Kwangju, Jeonnam, Republic of KoreaSearch for more papers by this authorKYUNG-YO KIM, KYUNG-YO KIM Wonkwang University Hospital, Kwangju, Jeonnam, Republic of KoreaSearch for more papers by this authorNYEON-HYOUNG AN, NYEON-HYOUNG AN Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of KoreaSearch for more papers by this authorKANG-MIN LEE, KANG-MIN LEE Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Jeonbuk, Republic of KoreaSearch for more papers by this authorHYUNG-MIN KIM, HYUNG-MIN KIM Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of KoreaSearch for more papers by this author JAE-YOUNG UM, JAE-YOUNG UM Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Jeonbuk, Republic of KoreaSearch for more papers by this authorJONG-CHEON JOO, JONG-CHEON JOO Wonkwang University Hospital, Kwangju, Jeonnam, Republic of KoreaSearch for more papers by this authorKYUNG-YO KIM, KYUNG-YO KIM Wonkwang University Hospital, Kwangju, Jeonnam, Republic of KoreaSearch for more papers by this authorNYEON-HYOUNG AN, NYEON-HYOUNG AN Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of KoreaSearch for more papers by this authorKANG-MIN LEE, KANG-MIN LEE Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Jeonbuk, Republic of KoreaSearch for more papers by this authorHYUNG-MIN KIM, HYUNG-MIN KIM Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of KoreaSearch for more papers by this author First published: 06 October 2003 https://doi.org/10.1034/j.1601-5223.2003.01605.xCitations: 1 Hyung-Min Kim, Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, South Korea. E-mail: [email protected] AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Sasang constitutional medicine is a major branch of Korean traditional oriental medicine. Constitutions of Sasang medicine refer to Taeyangin, Taeumin, Soyangin, and Soumin. The differences of disease severity to be shown in the constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction, CI, angiotensin converting enzyme (ACE) gene polymorphism, and Sasang constitutional classification. We investigated the association between ACE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang constitutional medicine. 208 CI patients and 643 controls without CI were examined. ACE genotype was determined by 7.5 % polyacrylamide gel separation after DNA amplification. The ACE/DD genotype was not associated with CI. The frequency of Taeumin of Sasang constitutional medicine in patients with CI was significantly higher than that in controls (χ2=41.202, p 0.05, data not shown). Table 1. Characteristics of CI patients and control subjects. Characteristics CI Patients Controls n 208 643 Age (year) 57.8±15.4 56.1±9.8 Male, % 55 55 Hypertension, % 45 45 Hypertension is defined as systolic blood pressure ≥160 or diastolic pressure ≥95 mm Hg, or receiving hypertensive medication. Values are means±S.D. Distribution of Sasang constitution Sasang constitutional classification was done by QSCC II program, and identified as Taeyangin, Taeumin, Soyangin and Soeumin, respectively. The distribution of each constitution in 208 patients with CI was as follows: Taeyangin, 0 (0 %); Taeumin, 124 (59.6 %); Soyangin, 63 (30.3 %); and Soeumin, 21 (10.1 %). It was significantly different from the distribution in 643 control subjects matched for age, gender, and history of hypertension with patients: Taeyangin, 0 (0 %); Taeumin, 237 (36.9 %); Soyangin, 228 (35.5 %); and Soeumin, 178 (27.7 %) (χ2=41.202, p<0.001) (Table 2). Table 2. Association between Sasang constitution and CI. Sasang constitutional classification1 Patients with CI n (%), n=208 Controls without CI n (%), n=643 Statistics 2 Taeumin 124(59.6) 237(36.9) χ2=41.202, p<.001 Soyangin 63(30.3) 228(35.5) Soeumin 21(10.1) 178(27.7) Taeyangin 0(0) 0(0) 1 Sasang constitutional classification was determined by QSCC II program. 2 χ2 test was used to test the association of Sasang constitution between patients with CI and controls. Genotype distribution of ACE I/D polymorphism The distribution of ACE genotype in 208 patients with CI was as follows: II, 66 (31.7 %); ID, 97 (46.6 %); and DD, 45 (21.6 %). It was not significantly different from the distribution in 643 control group: II, 231 (36.3 %); ID, 307 (48.3 %); and DD, 98 (15.4 %) (χ2=4.612, p>0.05) (Table 3). The genotype distribution of the gene in patients and control subjects did not deviate significantly from Hardy-Weinberg equilibrium. In the present study, there was no significant difference in ACE genotype distribution between CI patients and controls. However, the allele frequency in our study of a Korean population (I=0.60, D=0.40) was significantly different from those reported in French (I=0.41, D=0.59, χ2=22.63, p<0.05) (Rigat et al. 1990), Australian (I=0.48, D=0.52, χ2=15.64, p<0.05) (Zee et al. 1992), and Dutch ones (I=0.37, D=0.63, χ2=54.56, p 0.05) (Table 4). Table 4. Combined analysis of ACE genotypes and Sasang constitution in CI patients. ACE genotype Genotype Taeumin (n=124) Other constitutions (n=84) Statistics1 II 41(33.1) 25(29.8) NS2 ID+DD 83(66.9) 59(70.2) 1 χ2 test was used to test the association of ACE genotypes between Sasang constitutions in patients with CI. 2 NS, not significant. Discussion Studies concerning the relationship between gene polymorphisms potentially implicated cardiovascular disease are leading to conflicting findings, due in part, to the difference in ethnic background between populations. In this study, there was no difference between patients with CI and control groups, indicating that DD genotype was not a risk factor for CI in Korean population. However, we did find that the allele frequency in Koreans differed from those reported in French (Rigat et al. 1990), Australian (Zee et al. 1992), and Dutch populations (Schmidt et al. 1993), but were similar to those of Japanese (Ishigami et al. 1995) and Chinese populations (Lee 1994). The I/D polymorphism within intron 16 of the ACE gene was repeatedly shown to be associated with plasma ACE activity, although the mechanisms involved are still unknown (Rigat et al. 1990; Markus et al. 1995; Catto et al. 1996). This polymorphism might influence the tissue ACE activity, contributing to the pathological process disturbing the arterial wall integrity (Chrysant 1998). Brain infarction shows a familial aggregation (Diaz et al. 1986; Kiely et al. 1993; Graffagnino et al. 1994), suggesting that genetic factors influence the development of thrombotic brain infarction. Several studies reported a significant association between ACE gene polymorphism and brain infarction (Sharma et al. 1994; Markus et al. 1995; Kario et al. 1996; Seino et al. 1998). However, the Results of an association analysis of this polymorphism with CI are still controversial. In this study, we found no association between CI and ACE polymorphism in Koreans. This negative result is consistent with the Results previously reported in Taiwanese (Lin et al. 2000), while the result is not consistent with a Swedish (Kostulas et al. 1999) and an English report (Amar et al. 1998). The Sasang constitutional medicine we examined was established by Je-Ma Lee of Korea in 1894 (Lee 1996). Since then it has been developed as a major branch of Korean traditional oriental medicine, which occupies an important position along with Western medicine in Korea. It classifies people's constitutions into four types, such as Taeyangin, Taeumin, Soyangin and Soumin, according to the functions of the internal organs, behavioral characteristics, the symptoms of a disease, and quantitative variations including body size etc. Sasang constitution philosophy was supported the report demonstrating that continuous characters governed by a large number of independent mendelian factors (polygenic characters) would display precisely the quantitative variation and family correlations described by the biometrics (Fisher 1918). Also, Falconer extended the polygenic theory to discontinuous nonmendelian characters by postulating an underlying continuously variable susceptibility (Falconer 1981). We suggest that Sasang constitutional medicine is similar to the approach to complex diseases through the polygenic factors and nonmendelian characters by Fisher and Falconer. So, Sasang constitutional medicine could be applicable to whole world people as well as Korean and Asian. Also, Taeumin, who resembled the typical abdominal type of obesity in Western populations, is thought to have a higher rate of stroke, hypertension and hyperlipidemia than the other types because he or she has a large liver and small lungs. In the previous study, our group showed the regulatory effect of cytokine production in patients with CI by Yulda-Hanso-Tang, which is a prescription for the Taeumin patients with CI according to Sasang constitutional medicine (Shin et al. 2000). Here our data showed a consistent result with the viewpoint of Sasang constitutional medicine. Furthermore, the study of an association between Sasang constitution and CI has not been reported. Though we did not find significance between ACE polymorphism and Sasang constitution due to the small number of subjects and low statistical power, further studies are necessary to clarify the association with genetic factors. Korean traditional medicine has a long history of development. Although influenced by Chinese medicine, Korean traditional medicine has developed into an original system of traditional medicine that has surpassed the continental medical practice, sublimating itself into a native medical practice suitable to Korean lifestyles and physical constitutions. Sasang constitution medicine has been developed as a major branch of Korean traditional oriental medicine, which occupies an important position along with Western medicine in Korea. The present study is a first attempt to evaluate the efficacy of Korean traditional oriental medicine. Acknowledgements This research was supported by Wonkwang University in 2003. References Abbud Z.A., Wilson A.C., Cosgrove N.M. and Kostis J.B., (1998). Angiotensin-converting enzyme gene polymorphism in systemic hypertension. Am. J. Cardiol. 81: 244– 246. Amar K., MacGowan S., Wilcock G. et al., (1998). Are genetic factors important in the aetiology of leukoaraiosis? Results from a memory clinic population. Int. J. Geriatr. Psychiatry 13: 585– 590. Bloem L.J., Manatunga A.K., Boatright E. and Pratt J.H., (1993). Relation of race and a polymorphism in the angiotensin converting enzyme gene to enzyme levels. Hypertension 22: 407. Catto A., Carter A.M., Barrett J.H. et al., (1996). Angiotensin-converting enzyme insertion/deletion polymorphism and cerebro-vascular disease. Stroke 27: 435– 440. Chrysant S.G., (1998). Vascular remodeling: the role of angiotensin-converting enzyme inhibitors. Am. Heart J. 135: S21– S30. Diaz J.F., Hachinski V.C., Pederson L.L. and Donald A., (1986). Aggregation of multiple risk factors for stroke in siblings of patients with brain infarction and transient ischemic attacks. Stroke 25: 74– 78. Evans A.E., Poirier O., Kee F. et al., (1994). Polymorphisms of the angiotensin-converting enzyme gene in subjects who die from coronary heart disease. Q. J. Med. 87: 211– 214. Falconer D.S., (1981). Introduction to quantitative genetics, 2nd edn, Longman. Fisher R.A., (1918). The correlation between relatives under the supposition of mendelian inheritance. Trans. R. Soc. 52: 399– 433. Graffagnino C., Gasecki A.P., Doig G.S. and Hachinski V.C., (1994). The importance of family history in cerebrovascular disease. Stroke 25: 1599– 1604. Ishigami T., Iwamoto T., Tamura K. et al., (1995). Angiotensin I converting enzyme (ACE) gene polymorphism and essential hypertension in Japan. Ethnic difference of ACE genotype. Am. J. Hypertens. 8: 95– 97. Jeunemaitre X., Soubrier F., Kotelevtsev Y.V. et al., (1992). Molecular basis of human hypertension: role of angiotensinogen. Cell 71: 169– 180. Joseph K.K., (2001). Compass of health: using the art of sasang medicine to maximize your health, The Career Press, USA. Kario K., Kanai N., Saito K. et al., (1996). Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese hypertensives. Circulation 93: 1630– 1633. Kiely D.K., Wolf P.A., Cupples L.A. et al., (1993). Familial aggregation of stroke-the Framingham study. Stroke 24: 1366– 1371. Kostulas K., Huang W.X., Crisby M. et al., (1999). An angiotensin-converting enzyme gene polymorphism suggests a genetic distinction between ischaemic stroke and carotid stenosis. Eur J. Clin. Invest. 51: 478– 483. Ledru F., Blanchard D., Battaglia S. et al., (1998). Relation between severity of coronary artery disease, left ventricular function and myocardial infarction, and influence of the ACE I/D gene polymorphism. Am. J. Cardiol. 82: 160– 165. Lee E.J., (1994). Population genetics of the angiotensin-converting enzyme in Chinese. Br. J. Clin. Pharmac. 37: 212– 214. Lee J.M., (1996). In: Longevity & life preservation in oriental medicine, (ed. S. H. Choi), Kyung Hee Univ. Press, Korea. Lin J.J., Yueh K.C., Lin G.Y. et al., (2000). Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese. J. Formos. Med. Assoc. 99: 895– 901. Lindpaintner K., Pfeffer M.A., Kreutz R. et al., (1995). A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N. Engl. J. Med. 332: 706– 711. Markus H.S., Barley J., Lunt R. et al., (1995). Angiotensin-converting enzyme gene deletion polymorphism-a new risk factor for lacunar stroke but not carotid atheroma. Stroke 26: 1329– 1333. Miller S.A., Dykes D.D. and Polesky H.F., (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16: 1215. Rigat B., Hubert C., Alhenc-Gelas F. et al., (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J. Clin. Invest. 86: 1343– 1346. Schmidt S., Van Hooft I.M., Grobbee D.E. et al., (1993). Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: Dutch hypertension and offspring study. J. Hypertens. 11: 345– 348. Seino Y., Ikeda U., Maeda Y. et al., (1998). Angiotensin-converting enzyme gene polymorphism and plasminogen activator inhibitor 1 levels in subjects with cerebral infarction. J. Thromb. Thrombolysis 5: 263– 267. Sharma P., Carter N.D., Barley J. and Brown M.M., (1994). Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin I-converting enzyme. J. Hum. Hypertens. 8: 645– 648. Shin H.Y., Jeong H.J., Lee J.H. et al., (2000). Regulatory effect of cytokine production in patients with cerebral infarction by Yulda-Hanso-Tang. Immunopharmacol. Immunotoxicol. 22: 183– 193. Tiret L., Rigat B., Visvikis S. et al., (1992). Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am. J. Hum. Genet. 51: 197– 205. Ueda S., Weir C.J., Inglis G.C. et al., (1995). Lack of association between angiotensin converting enzyme and gene insertion/deletion polymorphism and stroke. J. Hypertens. 13: 1597– 1601. Vleming L.J., Van Der Pijl J.W., Lemkes H.H. et al., (1999). The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure I IDDM. Clin. Nephrol. 51: 133– 140. Wiemer G., Scholkens B.A., Becker R.H. and Busse R., (1991). Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension 18: 558– 563. Zee R.Y., Lou Y.K., Griffiths L.R. and Morris B.J., (1992). Association of a polymorphism of the angiotensin I converting enzyme gene with essential hypertension. Biochem. Biophys. Res. Commun. 184: 9– 15. Citing Literature Volume138, Issue3July 2003Pages 166-171 FiguresReferencesRelatedInformation