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Angiotensin Converting Enzyme Gene Polymorphism in Korean Hypertensive Adolescents

Angiotensin Converting Enzyme Gene Polymorphism in Korean Hypertensive Adolescents
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대학원 의학과
이화여자대학교 대학원
The essential role of renin-angiotensin system (RAS) in controlling blood pressure has been well established. Genes encoding components of the RAS have been proposed as candidate genes that determine genetic predisposition to hypertension and the risk of developing cardiovascular complications. The purpose of this study was to analyze angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphisms in Korean hypertensive adolescents and to determine the association between ACE genotype and cardiovascular risk. Forty hypertensive adolescents (16-17 years old, systolic blood pressure (BP) >140 mmHg and/or diastolic BP >90 mmHg) and a control group of twenty normotensive adolescents were included in the study. Obesity index (OI) and body mass index (BMI) were calculated by using individual height and weight. Skin fold thickness and arm circumference were also measured. Fat mass and fat distribution were analyzed by bioelectrical impedance. BP was measured at resting state by oscillometric methods. Serum aldosterone, renin, insulin, ACE, homocysteine, vitamin B12 and folate levels were evaluated after a fasting period of 12 hours. The carotid intima-media thickness (IMT) and carotid artery diameter were measured by carotid ultrasound. Pulse wave velocity (PWV) and ankle-brachial index (ABI) were also measured. Polymerase chain reaction (PCR) was conducted to amplify DNA from blood samples of each individuals to analyze ACE I/D polymorphism. Anthropometric data between two groups were significantly different: systolic BP was 149.9±7.9 mmHg in the hypertensive group vs 115.9±15.9 mmHg in the control group. Genotype frequencies of I/I were 37.5%, I/D 45.0% and D/D 17.5%. Serum ACE levels were 33.5±8.7 U/L in I/I genotype, 48.6±19.8 U/L in I/D genotype and 61.4±22.7 U/L in D/Dvi genotype, which showed that ACE levels were significantly higher in those with D/D or I/D genotype than in I/I genotype. Carotid IMT was significantly greater in D/D group than in I/I group. In conclusion, the D allele is associated with the increased level of ACE in Korean adolescents. In addition, D allele was associated with decreased compliance of carotid artery reflected by carotid IMT in this study.;레닌-안지오텐신계(Renin-Angiotensin System, RAS)가 혈압 조절에 있어 핵심적인 역할을 한다는 것은 이미 잘 알려진 사실이며 레닌-안지오텐신계의 구성 요소를 암호화하는 유전자가 고혈압의 유전적 감수성을 결정하고 심혈관계 합병증 발생에 중요한 역할을 할 것으로 생각된다. 본 연구에서는 고혈압 청소년에서 Angiotensin Convering Enzyme(ACE) 유전자 다형을 분석하고, 심혈관계 위험요인과의 연관성에 대하여 알아보고자 하였다. 16-17세의 수축기 혈압 140 mmHg, 이완기 혈압 90 mmHg 이상인 40명의 고혈압 청소년을 대상으로 하였으며, 같은 연령의 정상 혈압을 가진 20명의 청소년을 대조군으로 하였다. 신장과 체중을 측정하여 비만도와 체질량지수를 산출하였고, 피부 주름두께와 팔 둘레를 측정하였다. 안정된 상태에서 진동 혈압계를 이용하여 혈압을 측정하였고, bioelectrical impedance를 이용하여 체지방 질량, 체지방 분포를 측정하였다. 혈액 검사를 통하여 aldosterone, renin, insulin, ACE, homocysteine, vitamin B12, folate의 농도를 측정하였다. 경동맥 초음파로 경동맥 내피 두께를 측정하였고, Colin 사의 VP-1000을 이용하여 맥파 속도와 ankle brachial index(ABI)를 측정하였다. ACE 유전자 다형 분석은 RT-PCR과 전기영동을 통하여 분석하였다. 고혈압군과 대조군의 신체 계측치 사이에는 유의한 차이가 있었고, 두 군간의 수축기 혈압은 149.9±7.9 mmHg vs 115.9±15.9 mmHg 이었다. ACE 유전자 다형 분석에서 I/I 15명(37.5%), I/D 18명(45.0%), D/D 7명(17.5%)이었으며, 혈청 ACE 치는 각각 33.5±8.7 U/L, 48.6±19.8 U/L, 61.4±22.7 U/L로 I/I에 비하여 I/D와 D/D에서 유의하게 높았다. 경동맥 내피 두께는 I/I에 비해 D/D에서 유의하게 높았다(0.53±0.08 mm vs 0.65±0.10 mm). 본 연구에서는 D 대립유전자가 혈중 ACE 농도의 증가와 연관이 있었으며, D 대립유전자는 경동맥 내피 두께로 반영되는 경동맥의 유순도 감소와 연관이 있었다.
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