New insights of HLA class I association to Behçet’s disease in Portuguese patients (original) (raw)

HLA and non-HLA genes in Behçet’s disease: a multicentric study in the Spanish population

Arthritis Research & Therapy, 2013

Introduction: According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet's disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations. Methods: This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ 2 test.

Genetic Association of HLA-A*26, -A*31, and -B*51 with Behcet's Disease in Saudi Patients

Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders, 2016

Background HLA-B*51 has been universally associated with Behcet's disease (BD) susceptibility, while different alleles of HLA-A have also been identified as independent BD susceptibility loci in various ethnic populations. The objective of this study was to investigate associations of HLA-A and - B alleles with BD in Saudi patients. Materials and Methods Genotyping for HLA-A and HLA-B was performed using HLA genotyping kit (Lab type(R) SSO) in 120 Saudi subjects, including 60 BD patients and 60 matched healthy controls. Results Our results revealed that frequencies of HLA-A*26, -A*31, and - B*51 were significantly higher in BD patients than in controls, suggesting that HLA-A*26, -A*31, and - B*51 are associated with BD. The frequency of HLA-B*15 was significantly lower in BD patients than in controls. Stratification of genotyping results into active and nonactive forms of BD revealed that the frequency of HLA-A*31 was significantly higher in the nonactive form than in the active...

Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet’s disease

Tissue Antigens, 2008

Behc xet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5#-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5#-flanking region, exon and intron. However, seven polymorphisms were found in the 3#flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was

The HLA-B*51 Allele Is Strongly Associated With Behçet Disease in an Argentinean Population

Reumatología Clínica

Objective: To assess the association between the HLA-B*51 allele and Behç et Disease (BD) in Argentinean patients. Methods: We enrolled 34 consecutive Argentinean patients with definitive diagnosis of BD between October 2016 and March 2017. None of the patients had the HLA-B*51 allele determined at study entry. Unrelated controls (n = 240) were randomly obtained from the national cadaveric donor database. Demographic and clinical features of the patients were recorded by attending physicians through a questionnaire. Results: Mean age of cases was 42 years old. Nineteen (55.8%) were male, and the mean age at diagnosis was 35 years old; twenty (58.8%) were Mestizos, 8 (23.5%) were Caucasian, and 6 (17.6%) were Amerindians. Thirteen (38.2%) of 34 cases were HLA-B*51 allele positive; 11 were heterozygous and 2 homozygous for the allele. Thirty-four (14.2%) of 240 controls were positive for the HLA-B*51 allele. The association between BD and HLA-B*51 allele was greater than that of control group (OR = 3.75; p = 0.0012). Conclusions: The HLA-B*51 allele is strongly associated with BD in Argentinean patients. Our finding is consistent with previous studies indicating that the HLA-B*51 allele is an important susceptibility gene in BD regardless the geographical region and ethnicity.

Lack of association of HLA-B*51 with a severe disease course in Behcet's disease

Rheumatology, 2001

Objective. To investigate the previously reported association of HLA-B51 with the manifestations and severity of Behc Ëet's disease (BD). Methods. The study group consisted of 148 consecutive BD patients (89 male, 59 female) with a minimum disease duration of 5 yr followed up at an outpatient BD clinic in a tertiary referral centre. The patients were classi®ed into three severity groups (mild, moderate, severe) using a modi®ed form of the BD total activity index. HLA-B alleles were determined by DNA ampli®cation using the polymerase chain reaction and sequential hybridization with sequence-speci®c oligonucleotide probes. Results. The frequencies of genital ulceration wodds ratio (OR) = 3.1, 95% con®dence interval (CI) 1.3±7.5x, skin ®ndings (erythema nodosum, folliculitis or acne-like lesions) (OR = 4.4, 95% CI 1.1±17.7), a positive skin pathergy test (OR = 3.4, 95% CI 1.1±10.9) and eye disease (OR = 1.8, 95% CI 0.9±3.7) were all higher in B*51-positive patients. By contrast, no signi®cant association was observed between B*51 positivity and a severe disease course, and B*51 homozygosity did not exhibit a prominent association with the severity of BD. Male sex was found to be the strongest determinant of the severity of BD by logistic regression analysis (OR = 4.7, 95% CI 1.9±11.2). Conclusion. HLA-B*51 does not exhibit a strong association with a more severe disease course in BD. The involvement of other genetic anduor environmental factors seems to be required and to be more important than B*51 for the progression of BD.

HLA-B∗51 and B∗15 alleles confer predisposition to Behçet’s disease in Moroccan patients

Human Immunology, 2001

HLA class I polymorphism in Moroccan patients with Behçet's disease has not been investigated so far. In this study, HLA-B* phenotype frequencies were analyzed in 86 unrelated Moroccan patients (45 males, 41 females) and 111 ethnically matched healthy controls. The predisposing effect of the B*51 was confirmed (30.2% in patients and 15.3% in controls, OR ϭ 2.39, 95% CI [1.2-4.8], p ϭ 0.015). It was mostly observed in males with young age at disease onset (ORϭ 5.5 [1.9 -15.9], p ϭ 0.002 compared to controls). The Moroccan BD group also presented a previously unknown association with HLA-B*15 (25.6% of patients versus 11.7% of controls, OR ϭ 2.59 [1.2-5.5], p ϭ 0.014), both in females and in males with late-onset of the disease. Altogether, the B*15 and/or B*51 alleles were expressed in 55.8% of patients compared to 27% of controls (OR ϭ 3.4 [1.9 -6.2], p Ͻ 10-4, Pc ϭ 0.003). Our data indicate HLA-B effects on BD pathogenesis should be considered separately for men and women.

HLA-Cw*1602: a new susceptibility marker of Behçet's disease in southern Spain

Tissue Antigens, 1998

Abstract: Genotyping of the HLA-C locus by PCR-SSP in Behçet's disease patients from southern Spain reveals a statistically significant association with Cw*1602 (OR 20.15, corrected ρ<0.05). This is an uncommon allele absent from the healthy control group, which seems to confer higher relative risk than B51 in this study (OR 1.85). Stratified frequencies do not show statistically significant differences but suggest that the Cw*1602-B51 haplo-type could be the main HLA marker of Behçet's disease in the analyzed population.