HLA DRB1/DQB1 alleles and DRB1‐DQB1 haplotypes and the risk of rheumatoid arthritis in Tunisians: a population‐based case–control study

Lagha, Aymen; Messadi, Amira; Boussaidi, S; Kochbati, S.; Tazeghdenti, A; Ghazouani, Ezzedine; Almawi, WY; Yacoubi-Loueslati, Besma

doi:10.1111/tan.12855

Cited by 15 publications

(16 citation statements)

References 47 publications

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“…Corrected P-values were determined by multiplying individual P-values by the number of comparisons made at the locus level as previously described. [17][18][19] For each variant that was considered significantly associated with our outcomes using this method, multiple logistic regression was then employed to control for potential confounders. Pre-specified clinical variables-age, sex, abbreviated injury scale (AIS) scores for the head, spine, abdomen, and chest, and transfusion requirement-were included in the multiple logistic regression.…”

Section: Discussionmentioning

confidence: 99%

HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury

et al. 2020

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Objective: Determine whether variation in the HLA region is associated with the development of post-traumatic sepsis and septic shock. Background: Sepsis-related deaths remain a major source of mortality after traumatic injury. Genetic characteristics may contribute to susceptibility to adverse outcomes including sepsis and septic shock. Recent advances in nextgeneration sequencing technology now allow comprehensive genotyping of the HLA region. Methods: White adult trauma patients requiring more than 2 days of mechanical ventilation underwent HLA genotyping, and were followed for the development of sepsis and septic shock. Odds ratios (OR) for the associations between our outcomes and HLA variants were estimated, a correction for multiple comparisons was applied, and significant variants were included in regression models adjusting for potential confounders. Results: A total of 1184 patients were included. Patients were severely injured (median injury severity score 33); 33% developed sepsis, 6% septic shock, and in-hospital mortality was 14%. An amino acid variant (156Q) within the HLA-A peptide-binding groove was associated with greater odds of sepsis [OR 1.50,]. HLA-A Ã 02:01 was associated with lower odds of septic shock [OR 0.52, (0.32-0.82)]. These associations remained significant after adjusting for potential confounders. Conclusions: This is the first study to apply next-generation sequencing techniques to evaluate associations between immunogenetic factors and posttraumatic sepsis and septic shock. Associations with class I HLA variants are novel as they implicate adaptive immunity in post-traumatic sepsis. These findings are a step towards developing a panel of genetic markers assessing risk of infection-related complications as we move towards more personalized medicine.

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Section: Discussionmentioning

confidence: 99%

HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury

et al. 2020

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“…Fourteen studies reported the frequency of SS across autoimmune and other rheumatic conditions (Supplementary Table S7, http://links.lww.com/RHU/A253). 12,15,16,[18][19][20][21][24][25][26][27][29][30][31] The frequency of pSS ranged from 1.8% in a cross-sectional study from Morocco reporting data of 944 subjects with diverse autoimmune diseases recruited between 2010 and 2016, 29 to 47.6% in a cross-sectional study from Senegal reporting data of 27 subjects with systemic vasculitides recruited during 1995-2007. 16 Regarding sSS, the frequency in patients with RA ranged from 4.3% in a cross-sectional study conducted in Morocco during 2007-2011 and including 164 patients, 20 to 100% in the aforementioned study from Senegal, which included only 4 RA patients.…”

Section: Frequencymentioning

confidence: 99%

Epidemiology of Sjögren Syndrome in Africa

et al. 2022

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Background:The epidemiology of Sjögren syndrome (SS) has been extensively studied in America, Europe, and Asia.Objective: To summarize available data on the epidemiology of SS in Africa. Methods: MEDLINE, EMBASE, and African Journals Online were searched from inception up to May 17, 2020, to identify relevant articles. Data gleaned from these reports have been summarized narratively in this review.Results: Twenty-one hospital-based studies were included. These studies reported 744 cases of SS. The mean age at diagnosis varied between 28 and 73.6 years, and the female proportion ranged from 83.3% to 100%. There was no population-based incidence or prevalence. Among people with autoimmune and other rheumatic conditions, the frequency of primary SS was in the range 1.9% to 47.6%, whereas that of rheumatoid arthritisassociated secondary SS was in the range 4.3% to 100%. Sicca symptoms were the commonest features, with most frequently involved organs being joints, lungs, and neurological structures. Main autoantibodies were anti-Ro/SS antigen A, anti-La/SS antigen B, and antinuclear antibodies. Conclusions:The epidemiology of SS is poorly characterized in Africa.Available data are broadly consistent with those from other populations. Extensive and high-quality research is urgently needed.

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“…However, there are differences in the allelic frequency of certain HLA-DRB1 SE alleles across different populations. For instance, HLA-DRB1*04:01 and HLA-DRB1*04:04 alleles are common in RA patients with Caucasian ancestry, while HLA-DRB1*04:05 allele is common in the Asian population [3,6,7,9,[12][13][14][15]. It is also evident that the overall frequency of HLA-DRB1 SE alleles in Asian populations is lower than in Caucasian populations, despite the similar RA prevalence between these populations.…”

Section: Introductionmentioning

confidence: 99%

The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study

et al. 2021

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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.

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HLA DRB1/DQB1 alleles and DRB1‐DQB1 haplotypes and the risk of rheumatoid arthritis in Tunisians: a population‐based case–control study

Cited by 15 publications

References 47 publications

HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury

HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury

Epidemiology of Sjögren Syndrome in Africa

The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study

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