Dataset Information

Several regions in the major histocompatibility complex confer risk for anti-CCP-antibody positive rheumatoid arthritis, independent of the DRB1 locus.

ABSTRACT: Recent evidence suggests that additional risk loci for RA are present in the major histocompatibility complex (MHC), independent of the class II HLA-DRB1 locus. We have now tested a total of 1,769 SNPs across 7.5Mb of the MHC located from 6p22.2 (26.03 Mb) to 6p21.32 (33.59 Mb) derived from the Illumina 550K Beadchip (Illumina, San Diego, CA, USA). For an initial analysis in the whole dataset (869 RA CCP + cases, 1,193 controls), the strongest association signal was observed in markers near the HLA-DRB1 locus, with additional evidence for association extending out into the Class I HLA region. To avoid confounding that may arise due to linkage disequilibrium with DRB1 alleles, we analyzed a subset of the data by matching cases and controls by DRB1 genotype (both alleles matched 1:1), yielding a set of 372 cases with 372 controls. This analysis revealed the presence of at least two regions of association with RA in the Class I region, independent of DRB1 genotype. SNP alleles found on the conserved A1-B8-DR3 (8.1) haplotype show the strongest evidence of positive association (P ~ 0.00005) clustered in the region around the HLA-C locus. In addition, we identified risk alleles that are not present on the 8.1 haplotype, with maximal association signals (P ~ 0.001-0.0027) located near the ZNF311 locus. This latter association is enriched in DRB1*0404 individuals. Finally, several additional association signals were found in the extreme centromeric portion of the MHC, in regions containing the DOB1, TAP2, DPB1, and COL11A2 genes. These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles.

SUBMITTER: Lee HS

PROVIDER: S-EPMC2255558 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionCurrently there is limited data to drive clinical decision making regarding the choice of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARD); thus, head-to-head comparisons are needed to help guide prescribing. In recent years, significant advancements have helped clarify the mechanistic basis of the clinical associations of autoantibodies in rheumatoid arthritis (RA). This study evaluated the effectiveness of abatacept versus tofacitinib in anti-cyclic citrullinated peptide (CCP+) patients with rheumatoid arthritis (RA).MethodsCorEvitas (formerly known as CORRONA) Registry patients aged ≥ 18 years, who were CCP+ before initiating abatacept or tofacitinib (December 2012 onwards through October 2019), had 6-month follow-up data (baseline and 6-month Clinical Disease Activity Index [CDAI]), and were not in remission at index were included. Patients were frequency matched 1:1 by prior biologic use before propensity score matching (PSM). Primary (mean change [D] in CDAI) and secondary outcomes 6 months after index were compared using mixed-effects models adjusted for variables that remained unbalanced after PSM.ResultsFollowing PSM, most baseline characteristics for 291 patient pairs were well balanced between treatments, although fewer patients initiating abatacept versus tofacitinib received prior non-TNFi biologic DMARDs, and patients initiating abatacept versus tofacitinib had a higher physician global assessment score, patient-reported fatigue, and modified Health Assessment Questionnaire (mHAQ). In adjusted analyses, there were no significant differences in mean [D] from baseline in CDAI at 6 months with abatacept versus tofacitinib (P = 0.936). Patients naïve for b/tsDMARDs initiating abatacept had a numerically greater mean [D] in CDAI at 6 months versus tofacitinib, although this difference was not statistically significant (P = 0.662). There were no significant differences for any secondary outcomes.ConclusionsIn adjusted analyses, CCP+ patients with RA initiating treatment with abatacept versus tofacitinib did not show a statistically significant difference in reducing disease activity or improving patient-reported outcomes.

Dataset Information

Several regions in the major histocompatibility complex confer risk for anti-CCP-antibody positive rheumatoid arthritis, independent of the DRB1 locus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets