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Single nucleotide polymorphisms of ABCB1 gene and response to etanercept treatment in patients with ankylosing spondylitis in a Chinese Han population.

ABSTRACT: 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.

SUBMITTER: Yan RJ

PROVIDER: S-EPMC5293437 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphisms of ABCB1 gene and response to etanercept treatment in patients with ankylosing spondylitis in a Chinese Han population.

Yan Rui-Jian RJ Lou Ting-Ting TT Wu Yi-Fang YF Chen Wei-Shan WS

Medicine 20170201 5

<h4>Background</h4>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.<h4>Methods</h4>A total of 185 patients with AS in our hospital were r ...[more]

PMID: 28151874

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Project description:BACKGROUND: The human leukocyte antigen (HLA)-B27 gene is considered to be a major gene associated with predisposition to ankylosing spondylitis (AS); however, studies have demonstrated that non-HLA-B27 genes also contribute substantially to the susceptibility to AS. Two single nucleotide polymorphisms (SNPs), rs1004819 and rs10889677, of the interleukin-23 receptor (IL-23R) gene have been shown to be associated with AS susceptibility in European populations. However, ethnicity factors contribute to population splitting and genetic variation, and ethnic-specific genetic association studies are needed to validate these associations in patients from different ethnic backgrounds. This study therefore aimed to replicate the associations between these two SNPs and AS susceptibility in a Chinese Han population. METHODS: A total of 195 AS patients and 203 normal controls were recruited in this study. Two IL-23R gene SNPs, rs1004819 and rs10889677 were selected. Genotyping was performed in all subjects using the TaqMan probe method. Genotype and allele frequencies were compared between AS patients and normal controls by ?2 tests. RESULTS: There were no significant differences in either the genotype frequencies (TT 36.4%, TC 48.7% and CC 14.9% in AS patients; TT 35.0%, TC 50.0% and CC 15.0% in normal controls) or allele frequencies (T 60.8% and C 39.2% in AS patients; T 60.0% and C 40.0% in normal controls) of rs1004819 between AS patients and normal controls (P?>?0.05). In addition, both the genotype frequencies (AA 51.3%, AC 43.1% and CC 5.6% in AS patients; AA 57.6%, AC 35.5% and CC 6.9% in normal controls) and allele frequencies (A 72.8% and C 27.2% in AS patients; A 75.4% and C 24.6% in normal controls) of rs10889677 were also comparable between AS patients and normal controls (P?>?0.05). CONCLUSIONS: This study found no evidence for an association between either of the two previously identified AS-susceptibility IL-23R SNPs (rs1004819 and rs10889677) and onset of AS, indicating a possible difference in pathogenesis of AS between Chinese and European patients.

Dataset Information

Single nucleotide polymorphisms of ABCB1 gene and response to etanercept treatment in patients with ankylosing spondylitis in a Chinese Han population.

Publications

Single nucleotide polymorphisms of ABCB1 gene and response to etanercept treatment in patients with ankylosing spondylitis in a Chinese Han population.

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