HLA-B, DR and DQ antigens polymorphism in Tunisian patients with ankylosing spondylitis (a case–control study)

Abstract

The objective of the study is to assess the distribution of HLA-B genes, HLA-B27 subtypes, HLA-DRB1 and HLA-DQB1 alleles in patients with ankylosing spondylitis (AS) and in control subjects in the Tunisian population and to compare their distribution with that found in other countries. This is a case-control study that included 100 consecutive patients (85 males/15 females) with AS according to the modified New York criteria and 100 control individuals. HLA-B, B27 subtypes and class II (DR and DQ) typing of all subjects was performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). HLA-B27 was found in 62% of patients against 3% in controls (P = 0.0000, OR = 52.6, 15.6 < CI < 166.7). On the other hand, B*07 and B*51 were significantly decreased in comparison with controls (P = 0.01, OR = 0.3, 0.1 < CI < 0.8 and P = 0.0000, OR = 0.2, 0.1 < CI < 0.4, respectively). Eight B*27 subtypes were identified in the AS group, but the most frequent ones were B*2702 (32%) and B*2705 (24%). Among HLA-DRB1 alleles, a significant increase in DRB1*11 was found in comparison with controls (P = 0.01, OR = 2.2, 1.2 < CI < 4.5). However, DRB1*13 had a negative association with AS (P = 0.01, OR = 0.4, 0.2 < CI < 0.8). For HLA-DQB1 alleles, a significant positive association with DQB1*03 was observed in AS group (P = 0.03, OR = 1.8, 1.0 < CI < 3.4). Multivariate analysis by logistic regression revealed that DRB1*11 and DQB1*03 had no direct links with the disease, but were dependent on the presence of HLA-B27. Moreover, B*07 and B*51 seemed to have independently a negative correlation with AS, but DRB1*13 seemed to depend on B*51. Haplotypes carrying B27 were significantly associated with AS and those carrying B*07 or B*51 were negatively correlated with the disease. In conclusion, our study confirms that B27 predisposes to AS while B*07 and B*51 are negatively correlated with the disease.

Polymorphisms of HLA‐A, ‐B, ‐Cw and DRB1 antigens in Moroccan patients with ankylosing spondylitis and a comparison of clinical features with frequencies of HLA‐B*27

“…HLA‐B27 prevalence was low in healthy controls (3%), and only 6 alleles were found to be positive: 4 HLA‐B*2705 and 2 HLA‐B*2702 variants. Similar results have been reported by Kchir et al in Tunisian population, who studied 100 AS patients and 100 controls, and detected 8 HLA‐B27 subtypes in AS patients group (the most frequent were B*2705 and B*2702 ) and 3 HLA‐B27 alleles among 100 controls . Recently, Amribet et al identified only four HLA‐B*27 variants: B*2705, B*2702 , B*2703 , and B*2708 , among which B*2705 and B*2702 were the most frequent subtypes, in 54 Moroccan AS patients positive for B*27 .…”

HLA alleles and HLA‐B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population

“…B27/C*01 and B27/C*02 in Caucasian populations , B*27:05/C*02:022 and B*27:02/C*02:022 in Mexican, Spanish and Tunisian populations which reinforce our own results. Associations regarding HLA‐DRB1 and ‐DQB1 haplotypes are limited, however, B27/DRB1*11/DQB1*03 in the Tunisian population and B27/DRB1*07 in the British population have been reported . In these cases, the results were not in accordance with the significant haplotype identified by us.…”

Genetics in Ankylosing Spondylitis – Beyond HLA-B*27

“…This finding has been supported by the results obtained in different ethnic groups (Brown, et al, 1998a;Jaakkola, et al, 2006;Kchir, et al, 2010;Mahfoudh, et al, 2011;Ploski, et al, 1995;SaidNahal, et al, 2002;Sims, A M, et al, 2007). HLA-DRB1 was found to have a strong association with AS.…”

“…Within the same population, a casecontrol study reported a significant increase in HLA-DRB1*11 frequency among patients. It was also found a possible protective effect of HLA-DRB1*13 (Kchir, et al, 2010). DPA1*02:01, DPB1*13:01.…”