title: HLA DRB1/DQB1 alleles and DRB1-DQB1 haplotypes and the risk of rheumatoid arthritis in Tunisians: a population-based case-control study.
abstract: Rheumatoid arthritis (RA) is an inflammatory disease, which affects synovial joints, and is influenced by environmental and genetic factors, in particular the human leucocyte antigen (HLA) system. In our study, we investigated the association of HLA class II DRB1 and DQB1 alleles and DRB1-DQB1 haplotypes with RA susceptibility in Tunisian subjects. Therefore, HLA class II low-resolution genotyping was done in 110 RA patients and 116 controls, with a HLA-DRB1*04 high-resolution typing. Our results showed a strong association between HLA-DRB1*04/DRB1*04:05 alleles and RA presence, which persisted after correcting for multiple comparisons (Pc < 10-3, Pc = 0.020, respectively), in contrast to the protective effect of HLA-DRB1*04:03 allele (Pc = 15.2 × 10-4). However, increased frequency of DQB1*05 (Pc = 0.020) and decreased frequency of DRB1*04:03 subtype (Pc = 0.032) were seen in RF+ patients than controls. Moreover, when RA patients were compared to controls, DRB1*04-DQB1*03 haplotype was associated with RA susceptibility in Tunisians (Pc = 16.8 × 10-5), independently of RF status. Conversely, DRB1*01 allele and DRB1*01-DQB1*05 haplotype was highly present in RF+ vs RF- groups (Pc < 10-3, Pc = 5.6 × 10-3, respectively) and seems to be linked to seropositivity. Investigation of HLA class II alleles and haplotypes association with RA susceptibility with secondary Sjögren's syndrome (sSS) showed a predisposing effect of DRB1*04 (Pc < 10-3) and DRB1*04-DQB1*03 haplotype when RA with sSS/without sSS groups were compared to healthy controls. Our results confirms the association of HLA-DRB1*04, specifically HLA-DRB1*04:05 subtype, and DRB1*04-DQB1*03 haplotype with RA susceptibility in Tunisians, independently of seropositivity or the sSS presence.
authors: Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, University of Sciences of Tunis, Tunis, Tunisia.|Department of Immunology, Military Hospital of Tunis, Tunis, Tunisia.
authors: A
authors: A
authors: Lagha
authors: Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, University of Sciences of Tunis, Tunis, Tunisia.|Department of Immunology, Military Hospital of Tunis, Tunis, Tunisia.
authors: A
authors: A
authors: Messadi
authors: Department of Rheumatology, Habib Thameur Hospital, Tunis, Tunisia.
authors: S
authors: S
authors: Boussaidi
authors: Department of Rheumatology, Habib Thameur Hospital, Tunis, Tunisia.
authors: S
authors: S
authors: Kochbati
authors: Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, University of Sciences of Tunis, Tunis, Tunisia.
authors: A
authors: A
authors: Tazeghdenti
authors: Department of Immunology, Military Hospital of Tunis, Tunis, Tunisia.
authors: E
authors: E
authors: Ghazouani
authors: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors: W Y
authors: WY
authors: Almawi
authors: Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, University of Sciences of Tunis, Tunis, Tunisia.
authors: B
authors: B
authors: Yacoubi-Loueslati
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D014416:Tunisia
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: HLA class II polymorphism; haplotypes; rheumatoid arthritis; rheumatoid factors; secondary Sjögren's syndrome