PMID- 31165758
OWN - NLM
STAT- MEDLINE
DCOM- 20201029
LR  - 20210125
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Jun 5
TI  - Association of BUD13-ZNF259-APOA5-APOA1-SIK3 cluster polymorphism in 11q23.3 and 
      structure of APOA5 with increased plasma triglyceride levels in a Korean 
      population.
PG  - 8296
LID - 10.1038/s41598-019-44699-x [doi]
LID - 8296
AB  - In this association study on chromosome 11, the data from 12,537 Korean 
      individuals within the Health Examinee (HEXA) and the Korea Association Resource 
      (KARE) projects were analysed to identify genetic loci correlating with increased 
      and decreased plasma triglyceride (TG) levels. We identified a locus in 
      chromosomal region 11q23.3 that harbours genes BUD13, ZNF259, APOA5, APOA1, and 
      SIK3, which may be associated with plasma TG levels. In this locus, 13 relevant 
      single-nucleotide polymorphisms (SNPs) were found: rs184616707, rs118175510, 
      rs60954647, rs79408961, and rs180373 (near BUD13); rs11604424 (in ZNF259); 
      rs2075291, rs651821, and rs7123666 (in or near APOA5); rs525028 (near APOA1), and 
      rs645258, rs10160754, and rs142395187 (in or near SIK3). All 13 SNPs satisfied 
      the genome-wide significance level (P < 5.0 x 10(-8)) in both meta-analysis and 
      conditional analysis. Haplotype analysis of six SNPs (rs79408961, rs180373, 
      rs2075291, rs651821, rs525028, and rs10160754) that were selected based on the beta 
      coefficient and conditional P values, revealed nine common haplotypes (with 
      frequency 0.02-0.34) associated with both increased and reduced TG levels. 
      Furthermore, to shed light on possible structural implications, we modelled and 
      simulated the G185C variant of APOA5 (corresponding to rs2075291), which showed 
      the strongest association. Molecular dynamics simulation results showed that this 
      polymorphic variant of APOA5 has a different hydrogen bond network, increased 
      average distance between chains, and an ability to form distinct clusters. Owing 
      to the orientation of cysteine, the possibility of disulphide bond formation with 
      other proteins is evident. In summary, our association and modelling analyses 
      provided evidence that genetic variations in chromosomal region 11q23.3 are 
      associated with elevated TG levels.
FAU - Kim, Han-Kyul
AU  - Kim HK
AD  - Department of Molecular Science and Technology, Ajou University, Suwon, 16499, 
      Korea.
FAU - Anwar, Muhammad Ayaz
AU  - Anwar MA
AUID- ORCID: 0000-0002-8794-5589
AD  - Department of Molecular Science and Technology, Ajou University, Suwon, 16499, 
      Korea.
FAU - Choi, Sangdun
AU  - Choi S
AD  - Department of Molecular Science and Technology, Ajou University, Suwon, 16499, 
      Korea. sangdunchoi@ajou.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190605
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (APOA1 protein, human)
RN  - 0 (APOA5 protein, human)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Apolipoprotein A-V)
RN  - 0 (BUD13 homolog protein, human)
RN  - 0 (Disulfides)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Triglycerides)
RN  - 0 (ZPR1 protein, human)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (SIK3 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apolipoprotein A-I/*genetics
MH  - Apolipoprotein A-V/*genetics
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Disulfides
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Membrane Transport Proteins/*genetics
MH  - Middle Aged
MH  - Molecular Dynamics Simulation
MH  - Molecular Epidemiology
MH  - Polymorphism, Genetic
MH  - Prospective Studies
MH  - Protein Kinases/*genetics
MH  - RNA-Binding Proteins/*genetics
MH  - Republic of Korea/epidemiology
MH  - Triglycerides/*blood
PMC - PMC6549162
COIS- The authors declare no competing interests.
EDAT- 2019/06/06 06:00
MHDA- 2020/10/30 06:00
PMCR- 2019/06/05
CRDT- 2019/06/06 06:00
PHST- 2018/10/15 00:00 [received]
PHST- 2019/05/22 00:00 [accepted]
PHST- 2019/06/06 06:00 [entrez]
PHST- 2019/06/06 06:00 [pubmed]
PHST- 2020/10/30 06:00 [medline]
PHST- 2019/06/05 00:00 [pmc-release]
AID - 10.1038/s41598-019-44699-x [pii]
AID - 44699 [pii]
AID - 10.1038/s41598-019-44699-x [doi]
PST - epublish
SO  - Sci Rep. 2019 Jun 5;9(1):8296. doi: 10.1038/s41598-019-44699-x.