Please use this identifier to cite or link to this item:
Title: The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study
Authors: Tan, Lay Kim
Too, Chun Lai
Diaz Gallo, Lina Marcelo
Wahinuddin Sulaiman
Lau, Ing Seo
Heselynn Hussein
Nor Shuhaila Shahril
Gun, Suk Chyn
Eashwary, Mageswaran
Mohamed Said Mohd Shahrir
Ainon Mohd Mokhtar
Azmillah Rosman
Muhaini Othman
Shahnaz Murad
Alfredsson, Lars
Klareskog, Lars
Padyukov, Leonid
Keywords: HLA amino acid residues
HLA fine-mapping
Multi-ethnic Malaysian population
Rheumatoid arthritis
Risk variants
Issue Date: Dec-2021
Publisher: BioMed Central Ltd
Citation: Tan, L. K., Too, C. L., Diaz-Gallo, L. M., Wahinuddin Sulaiman, Lau, I. S., Heselynn Hussein, Nor Shuhaila Shahril, Gun, S. C., Mageswaran, E., Mohd Shahrir Mohamed Said, Ainon Mohd Mokhtar, Azmillah Rosman, Muhaini Othman, Shahnaz Murad., Alfredsson, L., Klareskog, L., & Padyukov, L. (2021). The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study. Arthritis Research & Therapy, 23(1).
Abstract: Background: Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy. Methods: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region. Results: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30–5.49, PGWAS = 7.22 × 10−29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37–0.62, PGWAS = 2.58 × 10−08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09–0.30, PGWAS = 1.60 × 10−09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia. Conclusions: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.
ISSN: 14786354
Appears in Collections:Journal Articles

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.