TITLE:
Meta-Analysis of the Association of HLA-DRB1 with Anti-Citrullinated Protein Antibody-Positive and Anti-Citrullinated Protein Antibody-Negative Rheumatoid Arthritis
AUTHORS:
Helin Feng, Jianfa Xu, Ning Zhang, Tianshu Gu, Lishi Wang, Cheng Tian, Yan Jiao, Karen Hasty, Weikuan Gu, Qingyi Liu
KEYWORDS:
Alleles, Anti-Citrullinated Protein Antibody, Hla -Drb1, Populations, Rheumatoid Arthritis
JOURNAL NAME:
Open Journal of Immunology,
Vol.6 No.4,
November
24,
2016
ABSTRACT: Because of genetic complex and variations of auto antibodies of rheumatoid arthritis
(RA) in different populations, the data on the association of HLA-DRB1 alleles in
anti-citrullinated protein antibody of (ACPA) RA were inconsistent. The purpose of
the study is to systematically summarize results of published data through performing
a meta-analysis using data in which HLA-DRB1 alleles are associated with ACPApositive
RA and ACPA-negative RA. In this study, we collected data from 12 studies
with 13,861 cases and 12,896 controls. Information in these studies included HLADRB1
typing and ACPA status from different countries. Odds ratios (ORs) and corresponding
95% confidence intervals (CI) were used to analyze the association of
different HLA-DRB1 alleles with ACPA-positive RA or ACPA-negative RA. To correct
skewing data, the analysis of ACPA-status was stratified by patient distribution.
Our analyses indicate that in ACPA-positive RA, all patients with RA had significantly
higher frequencies of HLA-DRB1*01, *04, *0401, *0405, *07, *11, *13 and *14
than controls. One of the HLA-DRB1*07, *11, *13 and *14 showed protective association
with RA. In addition, HLA-DRB1*03, *10 and *12 had more influence than
control to RA in European populations; the HLA-DRB1*03 and *12 alleles were associated
with the protection. In ACPA-negative RA, only DRB1*07 was associated
with the protection (OR 0.53 [95% CI 0.36 - 0.76]) among all HLA-DRB1 alleles in
European populations. In ACPA-positive RA, currently available results indicate that
*01, *04, *0401 and *0405 are susceptible, while HLA-DRB1*07, *11, *13 and *14 are protective in all populations. While the HLA-DRB1*10 is susceptible, HLA-DRB1*03
and *12 show protective association with RA in European populations. Additionally,
regardless of the positive or negative ACPA, the DRB1*07 is always associated with
protection in European populations.