title: Evaluation of polygenic cause in Korean patients with familial hypercholesterolemia - A study supported by Korean Society of Lipidology and Atherosclerosis.
abstract: OBJECTIVE
  Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in LDLR, APOB, or PCSK9. Polygenicity is a plausible cause in mutation-negative FH patients based on LDL cholesterol (LDL-C)-associated single nucleotide polymorphisms (SNPs) identified by the Global Lipids Genetics Consortium (GLGC). However, there are limited data regarding the polygenic cause of FH in Asians.
  
  
  METHODS
  We gathered data from 66 mutation-negative and 31 mutation-positive Korean FH patients, as well as from 2274 controls who participated in the Korean Health Examinee (HEXA) shared control study. We genotyped the patients for six GLGC SNPs and four East Asian LDL-C-associated SNPs and compared SNP scores among patient groups and controls.
  
  
  RESULTS
  Weighted mean 6- and 4-SNP scores (0.67 [SD = 0.07] and 0.46 [0.11], respectively) were both significantly associated with LDL-C levels in controls (p = 2.1 × 10(-4), R(2) = 0.01 and p = 5.0 × 10(-12), R(2) = 0.02, respectively). Mutation-negative FH patients had higher 6-SNP (0.72 [0.07]) and 4-SNP (0.49 [0.08]) scores than controls (p = 1.8 × 10(-8) and p = 3.6 × 10(-3), respectively). We also observed higher scores in mutation-positive FH patients compared with controls, but the difference did not reach statistical significance.
  
  
  CONCLUSIONS
  The present study demonstrates the utility of SNP score analysis for identifying polygenic FH in Korean patients by showing that small-effect common SNPs may cumulatively elevate LDL-C levels.
authors.affiliation: Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Manjae
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Cardiology Division, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea.
authors.forename: Do-Il
authors.initials: DI
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, South Korea.
authors.forename: Moo-Yong
authors.initials: MY
authors.lastname: Rhee
authors.affiliation: Cardiology Division, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Byoung-Kwon
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Heart Center of Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Ahn
authors.affiliation: Cardiology Division, Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University College of Medicine, Chunchon, South Korea.
authors.forename: Byung Ryul
authors.initials: BR
authors.lastname: Cho
authors.affiliation: Endocrinology Division, Department of Internal Medicine, Kyunghee University School of Medicine, Seoul, South Korea.
authors.forename: Jeongtaek
authors.initials: J
authors.lastname: Woo
authors.affiliation: Cardiology Division, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Hur
authors.affiliation: Cardiology Division, Department of Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, South Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Jeong
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University, South Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University, South Korea. Electronic address: shl1106@yuhs.ac.
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, South Korea. Electronic address: jihyni@yuhs.ac.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C573412:LDLR protein, human; D011973:Receptors, LDL; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Familial hypercholesterolemia; LDL-C score; Polygenic; Single nucleotide polymorphisms