| Backgrounds Human leukocyte antigen (HLA) A, B genes have been described as being involved in the susceptibility to TA in some populations. However, the association of HLA-A, B with TA has not been documented in the Chinese. The aim of this study was to explore the impact of HLA-A, B on the susceptibility of TA and long-term outcome.Methods HLA-A, B genotypes were performed by PCR-SSO method in 185 Chinese patients with TA and 466 unrelated healthy individuals. In this study a population based case-control study was used to analyze the association of the HLA-A, B genes with the development of TA in Chinese Han population. The impacts of HLA-A, B genes on the long-term outcome of TA were also evaluated furthermore. ResultsThe frequencies of A*32 (Pc< 0.01, OR=6.75, CI:3.72-12.33), B*13 (Pc<0.01, OR= 2.58, CI:1.76-3.80) and B*52 (Pc<0.01, OR=2.89, CI:1.70-4.89) were significantly increased in the TA patients compared to controls. The frequency of A* 11 among the TA patients were significantly lower than that among the controls (Pc<0.01, OR=0.42, CI: 0.27-0.67). The frequencies of the A*32-B*52 haplotype and the A*30-B*13 haplotype were significantly increased in the TA patients group (all Pc<0.01). The frequency of the A*11-B*40 haplotype was significantly increased in the control group (Pc<0.01). The mean age of onset in patients with B*13 was significantly earlier than the B*13 negative ones (22.8±7.3 years vs.26.0±9.0 years, P<0.01). The B*52 showed significant association with severity of TA after adjusted for age, gender and disease duration. The B*52 significantly increased the risk to develop major clinical events in TA (P<0.05,HR= 1.93, CI:1.10-3.40). ConclusionsThe HLA-A*32, B*13, B*52, A*30-B*13 and A*32-B*52 might increase susceptibility to TA while A*11 and A*11-B*40 might be a protective one in the Chinese Han population. The B*13 positive patients have the earlier onset age of the disease. The B*52 is associated with more severe clinical outcome and increasing the risk to develop major clinical events in TA. Which may be the important genetic predictor for TA severity and prognosis. BackgroundsTakayasu arteritis (TA) is a chronic large-vessel vasculitis that mainly affects the aorta and its major branches. The pathogenesis of TA is still unclear, but it is widely believed to be a genetic-related autoimmune disease. Tumor necrosis factor-a (TNF-α) is a multifunctional proinflammatory cytokine that might influence the pathogenesis of TA. However, there is still no evidence of the relationship between TNF-a gene promoter polymorphisms and TA.MethodsFive TNF-a gene promoter polymorphisms (-238G/A,-308G/A,-857C/T,-863C/A, and-1031C/T) were analyzed in 110 Chinese Han patients with TA, with a control group of 362 unrelated healthy individuals. Genotypes of TNF-a gene promoter polymorphisms were identified by direct sequencing. Plasma concentrations of TNF-a were determined by ELISA.ResultsOur results indicated that the frequency of the-863A allele was significantly lower in the TA patients than in the controls (18.2% vs.25.7%, P= 0.011), but the significance disappeared when given Bonferroni’s correct (Pc=0.55). The frequency of-863CA/AA genotypes was significantly lower in the refractory TA patients than in those with the 863CC genotype (22.4% vs.44.2%, Pc=0.01). The frequency of the GGCCT haplotype was significantly higher in patients than in the controls, whereas the frequency of haplotype GGCAT was significantly lower in patients than that in controls. The active patients had significantly increased TNF-a plasma levels (n=30,25.17 pg/mL,25th-75th percentiles, 9.54-38.36 pg/mL) compared with the remission patients (n=45,10.79 pg/mL,25th-75th percentiles,7.65-27.78 pg/mL) and controls (n=45,11.74 pg/mL,25th-75th percentiles, 8.04-16.48 pg/mL). The plasma TNF-a concentrations were significantly lower in the subjects carrying the-863A allele (n=15,9.55 pg/mL,25th-75th percentiles,5.67-13.59 pg/mL) than those without the A allele (n=30,13.13 pg/mL,25th-75th percentiles, 9.43-19.66 pg/mL) in healthy controls (P=0.037). The plasma TNF-a concentrations were also lower in the subjects carrying the-863A allele (n=15,8.05 pg/mL,25th-75th percentiles,6.89-14.19 pg/mL) than those without the A allele (n=30,15.59 pg/mL, 25th-75th percentiles,8.63-32.59 pg/mL) in remission patients (P=0.044). ConclusionsThe A allele of the -863C/A polymorphism is associated with decreased TNF-a expression in remission TA patients and controls in the Chinese Han population, which might influence the responses to medical therapy in TA. |
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