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 × 10-4, R2=0.01 and p=5.0 × 10-12, R2=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. 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.
|Number of pages||5|
|Publication status||Published - 2015 Sep 1|
Bibliographical noteFunding Information:
Financial support was provided by the Basic Science Research Program through the National Research Foundation of Korea, which was funded by the Ministry of Education, Science, and Technology (2012R1A1A2039828, 2012R1A4A1029061 to SH Lee) and the Creative Allied Project (Korean Research Council of Fundamental Science and Technology to SH Lee). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which was funded by the Ministry of Health & Welfare, Republic of Korea (Grant No.: HI14C0070 to JH Lee). This project was also supported by a Yonsei University College of Medicine student research grant to M Kwon.
This study was supported by the Korean Society of Lipidology and Atherosclerosis . This study was also provided with data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (4851-302), the and Korea Biobank Project (4851-307, KBP-2015-007), which were supported by the Korea Center for Disease Control and Prevention , Republic of Korea. We are grateful to Jiyeong Jeong, RN, for her assistance with clinical data collection and patient care, as well as Eun Suk Jung and Sewhi Kim for their support in genotype imputation and statistical analysis.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine