Clinical features of familial hypercholesterolemia in Korea: Predictors of pathogenic mutations and coronary artery disease - A study supported by the Korean Society of Lipidology and Atherosclerosis.
BACKGROUND
Proper screening and diagnosis of familial hypercholesterolemia (FH) is of critical importance for cardiovascular prevention. However, the clinical diagnosis of FH remains difficult partly because its phenotype can vary between different ethnicities. The aim of this study was to determine the clinical features and the best diagnostic approach in Korean FH patients. The predictors of putative pathogenic mutations and coronary artery disease (CAD) were also identified.


RESULTS
Ninety-seven patients with low-density lipoprotein-cholesterol >190 mg/dL and xanthoma or FH-compatible family history were included. Putative pathogenic mutations in LDLR, APOB, or PCSK9 genes were identified in 32% of the enrolled patients. The subjects were classified according to four sets of clinical criteria (Simon Broome, Dutch, MEDPED, Japanese). The mutation rates in definite type FH of Simon Broome or Dutch criteria were 35%-37% and lower in our patients than in those of other countries. The mutation detection rate by MEDPED criteria was 67%-75% and higher than those based on other criteria. The best low-density lipoprotein-cholesterol (LDL-C) threshold for predicting mutations was 225 mg/dL. LDL-C was found to be the only independent predictor of mutation carriers, while hypertension and low high-density lipoprotein-cholesterol were predictive of CAD.


CONCLUSIONS
The conventional clinical criteria showed limited mutation detection power and low specificities in Korean FH patients, in whom the best LDL-C threshold for putative mutation was 225 mg/dL. Traditional cardiovascular risk factors were also significantly associated with CAD risk in this population.
Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Dong Geum
DG
Shin
Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Soo Min
SM
Han
Cardiology Division, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
Doo Il
DI
Kim
Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
Moo-Yong
MY
Rhee
Division of Cardiology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Byoung-Kwon
BK
Lee
Heart Center of Chonnam, National University Hospital, Gwangju, Republic of Korea.
Young Keun
YK
Ahn
Cardiology Division, Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Republic of Korea.
Byung Ryul
BR
Cho
Endocrinology Division, Department of Internal Medicine, Kyunghee University School of Medicine, Seoul, Republic of Korea.
Jeong-Taek
JT
Woo
Cardiology Division, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea.
Seung-Ho
SH
Hur
Cardiology Division, Department of Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, Republic of Korea.
Jin-Ok
JO
Jeong
Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Cardiovascular Research Institute, Yonsei University Health System, Seoul, Republic of Korea.
Yangsoo
Y
Jang
Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: jihyni@yuhs.ac.
Ji Hyun
JH
Lee
Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Cardiovascular Research Institute, Yonsei University Health System, Seoul, Republic of Korea. Electronic address: shl1106@yuhs.ac.
Sang-Hak
SH
Lee
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics; D050197:Atherosclerosis / Q000208:ethnology* / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D012372:ROC Curve; D011973:Receptors, LDL / Q000235:genetics; D012044:Regression Analysis; D056910:Republic of Korea; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000235:genetics
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
Coronary artery disease; Diagnosis; Hyperlipoproteinemia type II; Mutation; Sensitivity and specificity