Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Angiotensinogen gene M235T polymorphism as a predictor of cardiovascular risk in hypertensive adolescents

고혈압 청소년의 심혈관계 위험요소로서 Angiotensinogen M235T 유전자 다형

  • Gil, Joo Hyun (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Lee, Jung Ah (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Park, Eun Young (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Hong, Young Mi (Department of Pediatrics, School of Medicine, Ewha Womans University)
  • 길주현 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 이정아 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 박은영 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 홍영미 (이화여자대학교 의학전문대학원 소아과학교실)
  • Published : 2009.01.15
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Abstract

urpose : The renin-angiotensin system (RAS) has been demonstrated to play a major role in regulating blood pressure. Therefore, components of the RAS are likely candidate genes that may predispose an individual to essential hypertension and cardiovascular complications. Among them, the M235T polymorphism of the angiotensinogen gene has been speculated to be associated with elevated circulating angiotensinogen concentrations and essential hypertension. This study aimed to analyze the angiotensinogen M235T polymorphism in hypertensive adolescents and investigate its relationship with cardiovascular risks. Methods : Forty Korean hypertensive adolescents (aged 16-17, systolic $BP{\geq}140 mmHg$ and/or diastolic $BP{\geq}90 mmHg$) and fifty seven normal adolescents were included. Obesity index (OI), body mass index (BMI) were calculated. BP was measured by oscillometric methods in resting state. Polymerase chain reaction (PCR) technique was performed on DNA from the hypertensives subjects to analyze the M235T polymorphism. Serum homocysteine, insulin, renin, aldosterone and angiotensin converting enzyme (ACE) were tested according to each genotype. The carotid intima-media thickness (IMT) and carotid artery diameter, Pulse wave velocity (PWV) and ankle-brachial index (ABI) were measured according to each genotype. Results : Genotype frequencies of T/T, M/T and M/M were 62.5%, 35.0%, 2.5%, respectively in hypertensive adolescents. The results were not significantly different compared to control group. Serum insulin, renin levels, BMI and OI were significantly higher in thoses with the M/M genotype as compared to those with the T/T of M/T genotype. Conclusion : This study showed that the M235T polymorphism was not associated with essential hypertension or any cardiovascular risks. Further clinical research is required to ascertain the relationship between this polymorphism and cardiovascular complications in Korean hypertensive adolescents.

목 적 : 레닌-안지오텐신계가 혈압 조절에 있어서 핵심적인 역할을 한다는 것은 이미 잘 알려진 사실이며, 이 체계의 한 구성 요소인 angiotensinogen을 암호화하는 유전자가 고혈압의 유전적 감수성을 결정하고 심혈관계 합병증 발생에 중요한 역할을 할 것으로 생각된다. 본 연구의 목적은 고혈압 청소년에서 angiotensinogen 유전자 다형을 분석하고, 특정 유전자형이 심혈관계 합병증의 예측 인자가 될 수 있는지를 알아보고자 하였다. 방 법 : 16세에서 17세 사이의 수축기 혈압 140 mmHg 이상이거나 이완기 혈압 90 mmHg 이상인 40명의 고혈압 청소년과 57명의 정상 청소년을 대상으로 하였다. 비만도, 체질량지수를 측정하였고, 안정된 상태에서 수축기, 이완기 혈압을 측정하였다. 호모시스테인, 인슐린, 레닌, 알도스테론, 안지오텐신 전환 효소(angiotensin convering enzyme, ACE)를 측정하였고, polymerase chain reaction (PCR)을 이용하여 angiotensinogen (M235T) 유전자형을 분석하였다. 경부 초음파로 경동맥 내중막 두께와 경동맥 직경을 측정하였고, 이를 이용하여 경동맥의 유순도와 신전도를 구하였다. VP-1000을 이용하여 pulse wave velocity (PWV)와 ankle-brachial index (ABI)를 측정하였다. 유전자 다형별로 각 계측치를 비교, 분석하였다. 결 과 : Angiotensinogen 유전자 다형 분석에서 T/T 군 25명(62.5%), M/T 군 14명(35%), M/M 군 1명(2.5%)로 정상 청소년과 유의한 빈도의 차이가 없었다. 고혈압군에서 인슐린, 레닌, 체질량지수, 비만도에서 세 유전형군 간의 유의한 차이가 나타났으나, 경동맥 내중막 두께와 직경, 신전도, 유순도, PWV, ABI에서는 세군 간의 유의한 차이는 없었다. 결 론 : Angiotensinogen의 특정 유전자 다형과 심혈관계 합병증간의 유의한 연관성은 없었으나, 본 연구의 고혈압 청소년 대상이 적었으므로 더 많은 연구가 필요할 것으로 생각된다.

Keywords

References

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