이혜순
2017-11-24T02:16:16Z
2017-11-24T02:16:16Z
2016-02
PLOS ONE, v. 11, NO 2, Article number e0150283, Page. 1-7
1932-6203
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150283
http://hdl.handle.net/20.500.11754/31832
The genetic association of HLA-DRB1 with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5) has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE.
This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1C1A1A02036527 to Dr. Kwangwoo Kim), the US National Institutes of Health (R01MD007909 and R01AR060366 to Dr. Swapan K. Nath), and the Korea Healthcare Technology R&D Project of the Ministry for Health & Welfare (HI13C2124 to Dr. Sang-Cheol Bae). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
en
PUBLIC LIBRARY SCIENCE
EXPRESSION
MHC
HLA-DR-BETA-1
INDIVIDUALS
HAPLOTYPE
MOLECULES
EXPLAIN
Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus
Article
2
11
10.1371/journal.pone.0150283
1-7
PLOS ONE
Kim, Kwangwoo
Bang, So-Young
Yoo, Dae Hyun
Cho, Soo-Kyung
Choi, Chan-Bum
Sung, Yoon-Kyoung
Kim, Tae-Hwan
Jun, Jae-Bum
Kang, Young Mo
Lee, Hye-Soon
2016007072
S
COLLEGE OF MEDICINE[S]
DEPARTMENT OF MEDICINE
lhsberon