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Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated
with Rheumatoid Arthritis and Systemic Lupus Erythematosus
#MMPMID26919467
Kim K
; Bang SY
; Yoo DH
; Cho SK
; Choi CB
; Sung YK
; Kim TH
; Jun JB
; Kang YM
; Suh CH
; Shim SC
; Lee SS
; Lee J
; Chung WT
; Kim SK
; Choe JY
; Nath SK
; Lee HS
; Bae SC
PLoS One
2016[]; 11
(2
): e0150283
PMID26919467
show ga
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.
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