Risk Of ACPA-positive Rheumatoid Arthritis Research Articles

Physical workload is associated with increased risk of rheumatoid arthritis: results from a Swedish population-based case–control study

ObjectivesThis study investigated: (1) the association of physical workload (PW) and risk of rheumatoid arthritis (RA); (2) the potential interactions between PW and the genes in the human leucocyte antigen...

Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case–control study

ObjectivesLung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA...

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations.

Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRβ1 at amino acid position 13, located outside the classical shared epitope (Pomnibus = 6.9 × 10(-135)). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr ≅ Gly > Ser)--but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional Pomnibus = 2.2 × 10(-33)) and 74 (conditional Pomnibus = 1.1 × 10(-8)). Outside of HLA-DRβ1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 × 10(-6)) and HLA-DPβ1 (Phe9, conditional P = 3.0 × 10(-5)) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. HLA-DRB1*09:01) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC.

THU0514 Thyroxin Substitution and the Risk of Developing Rheumatoid Arthritis; Results from the Swedish Population-Based Eira Study

BackgroundHypothyroidism is usually, in iodine-repleted areas, of autoimmune nature and leads to chronic thyroxin substitution. It shares some risk factors with anti-citrullinated-peptide antibodies (ACPA) positive rheumatoid arthritis (RA). 1,2ObjectivesWe asked...

Thyroxin substitution and the risk of developing rheumatoid arthritis; results from the Swedish population-based EIRA study

ObjectivesHypothyroidism in iodine-repleted areas is usually of autoimmune nature and leads to chronic thyroxin substitution. It shares some risk factors with anti-citrullinated peptide antibodies (ACPA)-positive rheumatoid arthritis (RA). We asked...

Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case–control study

We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18–70 years within a defined area of Peninsular Malaysia were evaluated in a case–control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9–9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3–2.0), compared with never-smokers. A significant dose–response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1–9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6–17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.

Shared Epitope Alleles Remain A Risk Factor for Anti-Citrullinated Proteins Antibody (ACPA) – Positive Rheumatoid Arthritis in Three Asian Ethnic Groups

BackgroundTo investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.Methods1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.ResultsThe proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.ConclusionThe HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

Contribution of Fcγ receptor IIIA gene 158V/F polymorphism and copy number variation to the risk of ACPA-positive rheumatoid arthritis

Background:Fcγ receptors (FcγRs) are potent immune modulators. FcγR genes encompass a complex region, polymorphic by both single nucleotide polymorphisms (SNPs) and copy number variation (CNV). The heterogeneity of rheumatoid arthritis...