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

Abstract

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.

Türkiye’nin Güneydoğu Anadolu Bölgesinde Tersiyer Bir Merkezdeki Romatoid Artritli Hastalarda HLAD-RB1 Alel Dağılımı

“…The relationship of the DRB1*0401 alleles with the predisposition to the disease in our study was in compliance with the studies conducted on Spanish (13), Greek (14) and Caucasian (15) populations, as well as the populations in various regions in Turkey (11,12). Similarly, the relationship of the DRB1*0408 subtype with the predisposition to RA in our study was in line with other studies conducted (15). However, the DRB1*01, DRB1*04, DRB1*0404 and DRB1*0405 alleles were not observed to have a statistically significant relationship with the disease in our region, although the frequency of these alleles was higher in patients with RA.…”

HLA-DRB1 Alleles Are Associated with the Susceptibility to Sporadic Parkinson’s Disease in Chinese Han Population

“…Several studies reported these alleles unequivocally associated with immune-related diseases [70]–[74]. The possibility cannot be ruled out that these alleles may be either susceptibility genes or linkage disequilibrium with other susceptibility genes contributing to the etiology of PD.…”

Smoking, the HLA-DRB1 shared epitope and ACPA fine-specificity in Koreans with rheumatoid arthritis: evidence for more than one pathogenic pathway linking smoking to disease

“…In Asian populations there are important differences in the prevalence of the various HLA-DRB1 SE alleles,16 17 and the RA-risk allele *0901, which lacks the SE motif, is found more commonly 16 18 19. Xue et al 20 found that the SE was associated with RA but not with ACPA production in a small Chinese RA cohort, whereas such associations have been reported in Malaysian, Chinese and Japanese patients 21 22. In a mixed Malaysian population, smoking, the SE and the interaction between them, only conferred risk for ACPA-positive RA 23.…”