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The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of  HLA-DRB1 ,  DQA1 ,  DQB1 , and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The  HLA-DRB1  shared epitope (SE)-encoding allele * 0405  displayed the most significant RA association ( P  = 1.35×10 −6 ) .  The grouped  DRB1  SE alleles showed great association with RA ( P  = 3.88×10 −13 ). The  DRB1  DRRAA alleles displayed significant protective effects ( P  = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive ( P  = 3.71×10 −13 ) and -negative RA ( P  = 3.89×10 −5 ). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.

HLA-DRB1 Shared Epitope-Dependent DR-DQ Haplotypes Are Associated with Both Anti-CCP–Positive and –Negative Rheumatoid Arthritis in Chinese Han