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Novel association between CDKAL1 and cholesterol efflux capacity: Replication after GWAS-based discovery

Authors
 Eun Jeong Cheon  ;  Do Hyeon Cha  ;  Sung Kweon Cho  ;  Hye-Min Noh  ;  Sungha Park  ;  Seok-Min Kang  ;  Heon Yung Gee  ;  Sang-Hak Lee 
Citation
 Atherosclerosis, Vol.273 : 21-27, 2018 
Journal Title
 Atherosclerosis 
ISSN
 0021-9150 
Issue Date
2018
Keywords
Atherosclerosis ; Cholesterol ; Genomics ; Lipoproteins ; Polymorphism ; Single nucleotide
Abstract
BACKGROUND AND AIMS: Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. METHODS: This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R(2) of overall model on CEC. RESULTS: In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. CONCLUSIONS: We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.
Full Text
https://www.sciencedirect.com/science/article/pii/S0021915018301965
DOI
10.1016/j.atherosclerosis.2018.04.011
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
Yonsei Authors
강석민(Kang, Seok Min) ORCID logo https://orcid.org/0000-0001-9856-9227
박성하(Park, Sung Ha) ORCID logo https://orcid.org/0000-0001-5362-478X
이상학(Lee, Sang Hak) ORCID logo https://orcid.org/0000-0002-4535-3745
지헌영(Gee, Heon Yung) ORCID logo https://orcid.org/0000-0002-8741-6177
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162213
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