PMID- 26160041 OWN - NLM STAT- MEDLINE DCOM- 20160609 LR - 20221207 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 242 IP - 1 DP - 2015 Sep TI - Evaluation of polygenic cause in Korean patients with familial hypercholesterolemia - A study supported by Korean Society of Lipidology and Atherosclerosis. PG - 8-12 LID - S0021-9150(15)30009-5 [pii] LID - 10.1016/j.atherosclerosis.2015.06.053 [doi] AB - BACKGROUND/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 x 10(-4), R(2) = 0.01 and p = 5.0 x 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 x 10(-8) and p = 3.6 x 10(-3), respectively). We also observed higher scores in mutation-positive FH patients compared with controls, but the difference did not reach statistical significance. CONCLUSION: 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. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Kwon, Manjae AU - Kwon M AD - Yonsei University College of Medicine, Seoul, South Korea. FAU - Han, Soo Min AU - Han SM AD - Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea. FAU - Kim, Do-Il AU - Kim DI AD - Cardiology Division, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea. FAU - Rhee, Moo-Yong AU - Rhee MY AD - Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, South Korea. FAU - Lee, Byoung-Kwon AU - Lee BK AD - Cardiology Division, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. FAU - Ahn, Young Keun AU - Ahn YK AD - Heart Center of Chonnam National University Hospital, Gwangju, South Korea. FAU - Cho, Byung Ryul AU - Cho BR AD - Cardiology Division, Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University College of Medicine, Chunchon, South Korea. FAU - Woo, Jeongtaek AU - Woo J AD - Endocrinology Division, Department of Internal Medicine, Kyunghee University School of Medicine, Seoul, South Korea. FAU - Hur, Seung-Ho AU - Hur SH AD - Cardiology Division, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea. FAU - Jeong, Jin-Ok AU - Jeong JO AD - Cardiology Division, Department of Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, South Korea. FAU - Jang, Yangsoo AU - Jang Y AD - 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. FAU - Lee, Sang-Hak AU - Lee SH AD - 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. FAU - Lee, Ji Hyun AU - Lee JH AD - Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, South Korea. Electronic address: jihyni@yuhs.ac. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150630 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (APOB protein, human) RN - 0 (Apolipoprotein B-100) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (LDLR protein, human) RN - 0 (Receptors, LDL) RN - 0 (Triglycerides) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Adult MH - Aged MH - Apolipoprotein B-100/*genetics MH - Asian People/*genetics MH - Cardiovascular Diseases/epidemiology MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Comorbidity MH - Diabetes Mellitus/epidemiology MH - Female MH - Genes, Dominant MH - Genotype MH - Humans MH - Hyperlipoproteinemia Type II/blood/ethnology/*genetics MH - Male MH - Middle Aged MH - *Multifactorial Inheritance MH - Mutation MH - Polymorphism, Single Nucleotide MH - Proprotein Convertase 9 MH - Proprotein Convertases/*genetics MH - Receptors, LDL/*genetics MH - Republic of Korea/epidemiology MH - Risk Factors MH - Serine Endopeptidases/*genetics MH - Triglycerides/blood OTO - NOTNLM OT - Familial hypercholesterolemia OT - LDL-C score OT - Polygenic OT - Single nucleotide polymorphisms EDAT- 2015/07/15 06:00 MHDA- 2016/06/10 06:00 CRDT- 2015/07/11 06:00 PHST- 2015/04/08 00:00 [received] PHST- 2015/06/24 00:00 [revised] PHST- 2015/06/24 00:00 [accepted] PHST- 2015/07/11 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2016/06/10 06:00 [medline] AID - S0021-9150(15)30009-5 [pii] AID - 10.1016/j.atherosclerosis.2015.06.053 [doi] PST - ppublish SO - Atherosclerosis. 2015 Sep;242(1):8-12. doi: 10.1016/j.atherosclerosis.2015.06.053. Epub 2015 Jun 30.