Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus

نویسندگان

  • Kwangwoo Kim
  • So-Young Bang
  • Dae Hyun Yoo
  • Soo-Kyung Cho
  • Chan-Bum Choi
  • Yoon-Kyoung Sung
  • Tae-Hwan Kim
  • Jae-Bum Jun
  • Young Mo Kang
  • Chang-Hee Suh
  • Seung-Cheol Shim
  • Shin-Seok Lee
  • Jisoo Lee
  • Won Tae Chung
  • Seong-Kyu Kim
  • Jung-Yoon Choe
  • Swapan K. Nath
  • Hye-Soon Lee
  • Sang-Cheol Bae
  • Jianming Tang
چکیده

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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عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2016