Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy / tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil.

BACKGROUND: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce. METHODS: The genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated. RESULTS: Lack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers. CONCLUSIONS: We did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.

Association of cytokine gene polymorphisms with hepatitis C virus infection in a population from Rio de Janeiro, Brazil.

BACKGROUND: The host immune response is an important indicator of the outcome of hepatitis C virus (HCV) infection and disease progression. The aim of this study was to explore cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV spontaneous clearance in a population from Rio de Janeiro, Brazil. METHODS: Genetic polymorphisms in the cytokines, tumor necrosis factor-alpha (-308), transforming growth factor-beta 1 (codons 10 and 25), interleukin-10 (IL-10; -1082 and -592), IL-6 (-174), and interferon-gamma (+874) were analyzed by polymerase chain reaction sequence-specific primers in 245 patients with chronic hepatitis C (CHC), 41 spontaneous recovery (SR) patients, and 189 healthy volunteers. Further, polymorphisms in IL-28B (rs12979860, rs12980275, and rs8099917) were assessed by real-time polymerase chain reaction in all groups. RESULTS: The IL-28B rs12979860 CC and rs12980275 AA genotypes were significantly associated with SR of HCV infection and response to therapy, whereas the C allele of IL-6 (-174) was associated with protection to CHC. A multivariate analysis showed that the male sex and IL-28B rs12979860 CT and TT and transforming growth factor-beta 1 (codon 10) TC genotypes were factors associated with CHC. Additionally, IL-6 (-174) C allele was increased in SR patients compared with patients with CHC. CONCLUSION: IL-28B polymorphisms are associated with spontaneous clearance of HCV and response to therapy in a Brazilian population. Also, IL-6 (-174) C allele is involved in SR and decreased inflammation scores.

HLA in a cohort of Brazilian patients with sarcoidosis.

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology. Hereditary etiology has been proposed as a cause of the sarcoidosis, and some Human Leucocyte Antigen (HLA) alleles have been related to the diagnosis or severity of the disease. Löfgren's syndrome has been linked to patients with the DRB1*03 allele, and non-resolving disease has been associated with the DRB1*07, DRB1*14 and DRB1*15 alleles. However, the results observed in Caucasian patients are not reproducible in other populations, such as in Japanese individuals. The aim of this study is to examine the HLA alleles in Brazilian patients with sarcoidosis confirmed by biopsy. Sixty-three patients were included in the study, and the HLA alleles were compared with 126 control individuals. HLA-A, -B, -C, -DRB1 and -DQB1 genes were typed using a Luminex Multi-analyte profiling system (One Lambda, Inc. Canoga Park, CA). Among sarcoidosis patients, the HLA A*23, A*80, B*08, B*41, DQB1*05 and DRB1*14 antigens tended to be more common than in the controls, whereas the B*44, B*45, B*51, B*58, DRB1*15 and DRB1*16 alleles were more frequently found in control subjects than in the sarcoidosis patients. However, after Bonferroni correction, only the HLA-DRB1*14 allele was found to be significantly different between sarcoidosis patients and controls (pC=0.0047, OR=11.69, CI=2.47-55.22). This allele was more frequent in mestizos and black patients. The presence of an HLA-DRB1*14 allele might determine the risk of sarcoidosis in Brazilian individuals, especially in mestizos and black patients.