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Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in south Tunisian patients

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Abstract

The aim of this study is to explore relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA) in the south Tunisian population. We studied 142 RA patients and 123 controls matched for age, sex, and ethnicity. HLA-DRB1 genotyping and HLA-DRB1*04 subtypes were performed using polymerase chain reaction/sequence-specific primers. Association was assessed based on the χ 2 test and odds ratio with 95% confidence interval. For multiple comparisons, p value was corrected (p c) with Bonferroni test. Two alleles, HLA-DRB1*04 (p = 0.045, p c  = NS) and HLA-DRB1*10 (p = 0.021, p c  = NS), were found to have increased frequencies in RA patients compared to controls. In contrast HLA-DRB1*08 allele was found to have a decreased frequency in patients compared to controls (p = 0.044, p c  = NS). Molecular subtyping of the most prevalent allele (DRB1*04) revealed increased frequencies of HLA-DRB1*04:05 in patients compared to controls (p = 0.013, p c  = NS) whereas HLA-DRB1*04:02 showed a protective effect (p = 0.005, p c  = 0.04). Moreover, stratified analyses indicated statistically significant associations between HLA-DRB1*04 allele and anti-cyclic peptides antibodies positivity (ACPA+) and rheumatoid factor positivity (RF+; p c  = 0.03, for both subgroups), HLA-DRBI*10 and ACPA+ and the presence of another autoimmune disease (p c  = 0.05 and p c  = 0.007, respectively), and HLA-DRB1*04:05 and RF+ and erosion (p c  = 0.005 and p c  = 0.049; respectively). A significant decrease in the frequency of the DRB1*04:02 allele was observed in patients with ACPA+ and RF+ subgroups (p c  = 0.04 and p c  = 0.02, respectively). Our results showed that there was a trend of positive association of HLA-DRB1*04 and HLA-DRB1*10 with RA as such and significant associations with the disease severity in the south Tunisian population.

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Acknowledgments

We thank Jeffrey Hammer (National Institutes of Health, Bethesda, Maryland 20892-2510, USA) for his critical reading of this manuscript. This work was supported by the Ministry of Higher Education and Scientific Research and the Ministry of Health, Tunisia.

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Authors and Affiliations

  1. Laboratory of Human Molecular Genetics, Faculty of Medicine, Avenue Majida Boulila, 3029, Sfax, Tunisia

    Mariem Ben Hamad, Faiza Fakhfakh & Abdellatif Maalej

  2. Laboratory Services, University Hospital Hedi Chaker, Sfax, Tunisia

    Nadia Mahfoudh, Arwa Kammoun, Lilia Gaddour, Faiza Hakim & Hafedh Makni

  3. Department of Internal Medicine, University Hospital Hedi Chaker, Sfax, Tunisia

    Sameh Marzouk & Zouheir Bahloul

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  1. Mariem Ben Hamad
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Correspondence to Mariem Ben Hamad.

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Ben Hamad, M., Mahfoudh, N., Marzouk, S. et al. Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in south Tunisian patients. Clin Rheumatol 31, 937–942 (2012). https://doi.org/10.1007/s10067-012-1954-z

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  • DOI: https://doi.org/10.1007/s10067-012-1954-z

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