Genetic Polymorphisms of Toll-like receptors 2 and 9 as Susceptibility Factors for the Development of Ankylosing Spondylitis and Psoriatic Arthritis.

INTRODUCTION: Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are classified as spondyloarthritis (SpA), a group of inflammatory rheumatic diseases with complex genetic etiology. Toll-like receptors (TLRs) have an important role in the mechanism of innate immunity and may influence inflammatory responses. Polymorphisms in TLR genes that lead to changes in these receptors or that interfere with the transcription rates of mRNA TLR may be involved in the chronic inflammatory immune response observed in SpA. Currently, there is a lack of studies associating genetic polymorphisms in TLRs and SpA. OBJECTIVE: Therefore, this case-control study is aimed at analyzing the influence of the respective SNPs on TLR2 rs5743708, TLR6 rs5743810, and TLR9 rs5743836 and rs187084 in the immunopathogenesis of SpA. METHODS: The polymorphisms genotyped by PCR-RFLP were TLR2 rs5743708, TLR6 rs5743810, and TLR9 rs5743836 and rs187084. The HLA-B ∗ 27 was performed by PCR-SSP. RESULTS: Logistic regression analysis showed a strong association between SNPs in TLR2 and TLR9 and susceptibility to SpA (OR = 12.56; CI = 6.5-25.9 and OR = 1.62; CI = 1.20-2.21, respectively). No association was observed among HLA-B ∗ 27 and TLR polymorphisms (p = 0.72), nor among BASDAI and TLR polymorphisms (p = 0.85). DISCUSSION: Our findings suggest that polymorphisms in TLR2 and TLR9 genes may contribute to the immunopathogenesis of the SpA. The rs187084, rs5743836, and rs5743708 polymorphisms were associated with the risk of SpA development, in this study, and lead to significant changes in the innate and adaptive immune response profile, as well as the maintenance of the regulation of immunological mechanisms. CONCLUSION: The polymorphism rs5743708 for the TLR2 and the rs187084_rs5743836 TLR9 haplotypes appear to be involved in the development of clinical forms of SpA and can be a possible therapeutic target for the spondyloarthritis.

HLA-A, -B, -DRB1, -DQA1, and -DQB1 profile in a population from southern Brazil.

The aim of this study was to determine the allele and haplotype frequencies of HLA-A, -B, -DRB1, and -DQB1 in a self-declared White population from the north and northwestern state of Paraná, southern Brazil, and compare the data with populations worldwide. The genotyping was performed with a group of 641 individuals, based on PCR-SSO and -SSP methods, and allele and haplotype frequencies were estimated. Comparisons with European, African, Asian, and Amerindian populations were performed. The most frequent allelic groups, alleles and haplotypes were: HLA-A*02, HLA-B*35, HLA-DRB1*07:01, HLA-DQB1*03:01, and HLA-A*01/B*08/DRB1*03:01. The results reinforced a predominance of a European composition in the self-declared White population from the north and northwestern Paraná.

Influence of TNF and IL17 Gene Polymorphisms on the Spondyloarthritis Immunopathogenesis, Regardless of HLA-B27, in a Brazilian Population.

BACKGROUND AND OBJECTIVES: Spondyloarthritis (SpA) represents a heterogeneous group of immune-mediated inflammatory diseases that have overlapping clinical features, genetic predisposition, and pathogenic mechanisms. Hence, we investigated, through a case-control study, whether single-nucleotide polymorphisms of TNF and IL17 genes are associated with SpA, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in a mixed Brazilian population. METHODS: Genotyping of TNF-308 (rs1800629), TNF-238 (rs361525), IL17A (rs2275913), IL17F (rs763780), and HLA-B27 polymorphisms was performed in 243 patients with SpA and 210 controls from Southern Brazil using SSOP-Luminex (One Lambda) and PCR-SSP assays. RESULTS: Significant associations were confirmed between the HLA-B27 marker and SpA, AS, and PsA diseases. While TNF-308 (rs1800629) AA/GA, IL17A (rs2275913) AA/GA, and IL17F (rs763780) CC/TC genotype frequencies were associated, in the dominance inheritance model, with SpA and AS, regardless of gender, the presence of HLA-B27, TNF-238 (rs361525) GA/AA, IL17A (rs2275913) AA/GA, and IL17F (rs763780) genotypes was associated with PsA. CONCLUSION: In this Brazilian population, TNF and IL17 gene polymorphisms responsible for the expression of important inflammatory cytokines were associated with overall SpA, and, specifically, with AS and PsA, regardless of gender and HLA-B27. However, future larger studies with different ethnicities may be necessary to confirm these genetic associations.

HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance.

BACKGROUND: Many epidemiological studies have shown that the genetic factors of the host play a role in the variability of clinical response to infection caused by M. leprae. With the purpose of identifying genes of susceptibility, the present study investigated the possible role of HLA-DRB1 and DQA1/DQB1 alleles in susceptibility to leprosy, and whether they account for the heterogeneity in immune responses observed following infection in a Southern Brazilian population. METHODS: One hundred and sixty-nine leprosy patients and 217 healthy controls were analyzed by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers (One Lambda, CA, USA). RESULTS: There was a positive association of HLA-DRB1*16 (*1601 and *1602) with leprosy per se (7.3% vs. 3.2%, P = 0.01, OR = 2.52, CI = 1.26-5.01), in accord with previous serological studies, which showed DR2 as a marker of leprosy. Although, HLA-DQA1*05 frequency (29.8% vs. 20.9%, P = 0.0424, OR = 1.61, CI = 1.09-2.39) was higher in patients, and HLA-DQA1*02 (3.0% vs. 7.5%, P = 0.0392, OR = 0.39, CI = 0.16 - 0.95) and HLA-DQA1*04 (4.0% vs. 9.1%, P = 0.0314, OR = 0.42, CI = 0.19 - 0.93) frequencies lower, P-values were not significant after the Bonferroni's correction. Furthermore, HLA-DRB1*1601 (9.0% vs. 1.8%; P = 0.0016; OR = 5.81; CI = 2.05-16.46) was associated with susceptibility to borderline leprosy compared to control group, and while HLA-DRB1*08 (11.2% vs. 1.2%; P = 0.0037; OR = 12.00; CI = 1.51 - 95.12) was associated with susceptibility to lepromatous leprosy, when compared to tuberculoid leprosy, DRB1*04 was associated to protection. CONCLUSION: These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy per se, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.