1. Kor /
  2. Eng

  1. Kor /
  2. Eng

Major AchievementsFollowings are the major outstanding achievements of the SAIHST faculties

[원홍희 교수/우수논문] J Am Coll Cardiol. 2016 Mar 28. pii: S0735-1097(16)32399-3.
No 15
Date 2016/04/19





원홍희 교수

(SAIHST 디지털헬스학과 조교수)


Impact Factor('14) = 16.503




J Am Coll Cardiol. 2016 Mar 28. pii: S0735-1097(16)32399-3. doi: 10.1016/j.jacc.2016.03.520. [Epub ahead of print]


Diagnostic Yield of Sequencing Familial Hypercholesterolemia Genes in Patients with Severe Hypercholesterolemia. 

Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, van Leeuwen EM, Natarajan P, Emdin CA, Bick AG, Morrison AC, Brody JA, Gupta N, Nomura A, Kessler T, Duga S12, Bis JC, van Duijn CM, Cupples LA, Psaty B, Rader DJ, Danesh J, Schunkert H, McPherson R, Farrall M, Watkins H, Lander E, Wilson JG, Correa A, Boerwinkle E, Merlini PA, Ardissino D, Saleheen D, Gabriel S, Kathiresan S.






About 7% of US adults have severe hypercholesterolemia (untreated LDL cholesterol ≥190 mg/dl). Such high LDL levels may be due to familial hypercholesterolemia (FH), a condition caused by a single mutation in any of three genes. Lifelong elevations in LDL cholesterol in FH mutation carriers may confer CAD risk beyond that captured by a single LDL cholesterol measurement. 



Assess the prevalence of a FH mutation among those with severe hypercholesterolemia and determine whether CAD risk varies according to mutation status beyond the observed LDL cholesterol.



Three genes causative for FH (LDLR, APOB, PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD cases, 8,577 CAD-free controls) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database.



Among 8,577 CAD-free control participants, 430 had LDL cholesterol ≥190 mg/dl; of these, only eight (1.9%) carried a FH mutation. Similarly, among 11,908 participants from 5 prospective cohorts, 956 had LDL cholesterol ≥190 mg/dl and of these, only 16 (1.7%) carried a FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers when compared with non-carriers. When compared to a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had six-fold higher risk for CAD (OR 6.0; 95%CI 5.2–6.9) whereas those with LDL cholesterol ≥190 mg/dl as well as a FH mutation demonstrated twenty-two fold increased risk (OR 22.3; 95%CI 10.7–53.2).



Among individuals with LDL cholesterol ≥190 mg/dl, gene sequencing identified a FH mutation in <2%. However, for any given observed LDL cholesterol, FH mutation carriers are at substantially increased risk for CAD.


familial hypercholesterolemia;
low-density lipoprotein cholesterol;
gene sequencing;
coronary artery disease;



(출처_Science Direct)


원홍희 교수 연구 소개  [프로필 보기]  

     본 연구실은 생물정보학, 통계학, 기계학습 등의 다양한 기법을 적용하여 대규모 유전체 데이터와EMR로부터 추출한 임상 데이터를 연계하여 다양한 인간 질환의 원인이 되는 유전 변이 및 유전자를 발굴함. 또한, 환자의 유전 프로파일 및 건강 프로파일을 통합하여 질병을 조기에 탐지하고, 예방하며, 맞춤화된 치료를 제안할 수 있는 시스템을 개발함. 본 연구실은 유전체학, 생물정보학, 데이터분석 분야에서 Nature, New England Journal of Medicine, Nature Genetics에 연구 결과를 발표하였고, 30편 이상의 국제논문을 출판함.


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