RT Journal Article
SR Electronic
T1 A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 2134
OP 2139
DO 10.1136/annrheumdis-2011-200353
VO 70
IS 12
A1 Terao, Chikashi
A1 Ohmura, Koichiro
A1 Kochi, Yuta
A1 Ikari, Katsunori
A1 Maruya, Etsuko
A1 Katayama, Masaki
A1 Shimada, Kota
A1 Murasawa, Akira
A1 Honjo, Shigeru
A1 Takasugi, Kiyoshi
A1 Matsuo, Keitaro
A1 Tajima, Kazuo
A1 Suzuki, Akari
A1 Yamamoto, Kazuhiko
A1 Momohara, Shigeki
A1 Yamanaka, Hisashi
A1 Yamada, Ryo
A1 Saji, Hiroo
A1 Matsuda, Fumihiko
A1 Mimori, Tsuneyo
YR 2011
UL http://ard.bmj.com/content/70/12/2134.abstract
AB Background HLA-DRB1 is associated with rheumatoid arthritis (RA). However, it has recently been suggested that HLA-DRB1 is only associated with patients with RA who have anticitrullinated peptide/protein antibodies (ACPA), which are specific to RA. Objective To elucidate whether specific HLA-DR alleles are associated with ACPA-negative RA development. Methods HLA-DRB1 typing was carried out in 368 Japanese ACPA-negative patients with RA and 1508 healthy volunteers as the first set, followed by HLA-DRB1 typing of 501 cases and 500 controls as the second set. The HLA-DRB1 allele frequency and diplotype frequency were compared in each group, and the results of the two studies were combined to detect HLA-DRB1 alleles or diplotypes associated with ACPA-negative RA. Results HLA-DRB1*12:01 was identified as a novel susceptibility allele for ACPA-negative RA (p=0.000088, OR=1.72, 95% CI 1.31 to 2.26). HLA-DRB1*04:05 and *14:03 showed moderate associations with ACPA-negative RA (p=0.0063, OR=1.26, 95% CI 1.07 to 1.49 and p=0.0043, OR=1.81, 95% CI 1.20 to 2.73, respectively). The shared epitope was weakly associated with ACPA-negative RA, but no dosage effect was detected (p=0.016, OR=1.17, 95% CI 1.03 to 1.34). A combination of HLA-DRB1*12:01 and DRB1*09:01 showed a strong association with susceptibility to ACPA-negative RA (p=0.00013, OR=3.62, 95% CI 1.79 to 7.30). Homozygosity for HLA-DR8 was significantly associated with ACPA-negative RA (p=0.0070, OR=2.16, 95% CI 1.22 to 3.82). It was also found that HLA-DRB1*15:02 and *13:02 were protective against ACPA-negative RA (p=0.00010, OR=0.68, 95% CI 0.56 to 0.83 and p=0.00059, OR=0.66, 95% CI 0.52 to 0.84, respectively). Conclusions In this large-scale association study multiple alleles and diplotypes were found to be associated with susceptibility to, or protection against, ACPA-negative RA.