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Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis.

ABSTRACT: The successful therapeutic use of anti-TNF biological agents in patients with ankylosing spondylitis (AS) indicates that tumor necrosis factor-? (TNF-?) and tumor necrosis factor receptor (TNFR) genes are involved in the pathogenesis of AS. TNF-? exerts its biological activity by binding to its cell surface receptors (p55 TNF-? receptor [TNFRI, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A)] and p75 receptor [TNFRII, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1B (TNFRSF1B)]. TNFRSF1A and TNFRSF1B may be related to AS, but the relevant studies are still limited. Therefore, we aim to explore the association between TNFRSF1A and TNFRSF1B polymorphisms and susceptibility and short- and long-term response to anti-TNF treatment in human leukocyte antigen-B27 (HLA-B27)-positive Chinese Han patients with AS.A total of 215 HLA-B27-positive patients with AS and 216 HLA-B27-positive matched controls were enrolled and genotyped for rs767455, rs2234649, and rs1061622. A subset of 50 AS patients was also studied for the association of these polymorphisms with the short- and long-term response to etanercept assessed by Assessment in Ankylosing Spondylitis 20 (ASAS20) and Assessment in Ankylosing Spondylitis 40 (ASAS40).Our data showed that rs767455 was associated with the susceptibility of AS, G allele of rs767455 exhibited an association with the risk of developing AS (OR?=?1.63 (1.04-2.55), P?=?.032). Rs1061622 polymorphism was associated with total back pain and chest expansion. Only rs1061622 was significantly associated with long-term efficacy of etanercept: the TG genotype of rs1061622 worsened ASAS20 and ASAS40 responses at 12 months (P?=?.021 and .041, respectively).The results suggest that TNFRSF1A and TNFRSF1B polymorphisms were associated with susceptibility, severity, and the long-term therapeutic efficacy of etanercept of patients with AS.

SUBMITTER: Xing-Rong W

PROVIDER: S-EPMC6081148 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis.

Xing-Rong Wang W Sheng-Qian Xu X Wen Liu L Shan Qi Q Fa-Ming Pan P Jian-Hua Xu X

Medicine 20180801 31

The successful therapeutic use of anti-TNF biological agents in patients with ankylosing spondylitis (AS) indicates that tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor (TNFR) genes are involved in the pathogenesis of AS. TNF-α exerts its biological activity by binding to its cell surface receptors (p55 TNF-α receptor [TNFRI, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A)] and p75 receptor [TNFRII, encoded by the Tumor Necrosis Factor Receptor S ...[more]

PMID: 30075559

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Project description:Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese.Four ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters.The SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P <0.00001, OR 1.38, 95% CI: 1.12 to 1.58) in Taiwanese.This study provides the first evidence of ERAP1 SNPs involving syndesmophyte formation. The interactions between ERAP1 SNPs and HLA-B27 play critical roles in pMHC I pathway processing contributing to the pathogenesis of AS in multiple populations.

Project description:Etanercept was highly recommended for patients with ankylosing spondylitis (AS), as its efficacy has been confirmed in AS, while genetic polymorphisms, by affecting drug metabolism or drug receptor, lead to interindividual variability in drug disposition and efficacy. Therefore, this study aims to investigate whether ABCB1 gene polymorphisms can predict therapeutic response to etanercept in patients with AS.A total of 185 patients with AS in our hospital were recruited into our study from December 2012 to May 2015. The frequency distributions of genotype and allele of rs2032582, rs1128503, and rs1045642 were detected by polymerase chain reaction (PCR) and electrophoresis verification enzyme products method. AS patients received etanercept treatment for 12 weeks, followed by this would be evaluated by the bath AS disease activity index (BASDAI) score improvement and the assessment of spondyloArthritis international society 20/50/70 (ASAS20/50/70) score improvements to explore the relationship between genotype of ABCB1 gene polymorphisms and therapeutic response to etanercept in patients with AS.After 12 weeks, the BASDAI score mean improvement value of rs2032582 A/A genotype was 2.87?±?0.52. The ratios of patients with rs2032582 A/A genotype reaching the BASDAI50 and ASAS20 evaluation criteria were 64.29% and 92.86%, respectively. The results indicated that efficacy of etanercept was promoted in rs2032582 A/A genotype. The BASDAI score mean improvement value of rs1128503 C/C genotype was 2.79?±?0.54 after 12 weeks. The ratios of patients with rs1128503 C/C genotype reaching the BASDAI50 and ASAS20 evaluation criteria were 66.67% and 93.94%, respectively. The results indicated that efficacy of etanercept was promoted in rs1128503 C/C genotype. However, no significant associations were observed between rs1045642 and therapeutic response to etanercept in AS patients.ABCB1 gene rs2032582 and rs1128503 polymorphisms may be associated with the efficacy of etanercept in AS patients. ABCB1 gene polymorphisms can act as biological indicators of etanercept efficacy.

Dataset Information

Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis.

Publications

Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis.

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