title: Characteristics of A20 gene polymorphisms and clinical significance in patients with rheumatoid arthritis.
abstract: BACKGROUND
  There are a number of studies regarding to the susceptibility of A20 SNPs in rheumatoid arthritis (RA); however, a few of these studies have shown an association between polymorphisms in the A20 gene and RA risk in the Chinese population. The aim of this study was to investigate the characteristics of A20 gene polymorphisms, the association between polymorphisms and clinical significance in Chinese RA patients.
  
  
  METHODS
  PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) (50 cases), synovial fluid (11 cases) from RA patients and PBMCs from 30 healthy individuals. Quantitative Real-time PCR (qRT-PCR) was used to analyze the A20 mRNA expression in 38 RA patients and 40 healthy individuals. Pearson's Chi square test and two independent-samples Wilcoxon tests were used for statistical analysis.
  
  
  RESULTS
  Eight single nucleotide polymorphisms (SNPs) (rs5029937, rs3799491, rs598493, rs2307859, rs146534657, rs2230926, rs661561, and rs582757) were identified in PBMCs of RA patients. One new mutation (14284 T > A) was identified in synovial fluid mononuclear cells from one RA case. rs146534657 was identified for the first time in two RA cases. Patients with rs146534657 (12411 A > G, Asn102Ser) AG genotype or rs2230926 (12486 T > G, Phe127Cys) TG genotype had poor outcome. Significantly lower A20 mRNA expression was found in PBMCs from RA patients compared with healthy individuals (p < 0.001). There was a higher A20 mRNA expression in RA patients with rs2230926 TG genotype and rs146534657 AG genotype (11.56 ± 7.39) than patients with rs2230926 TT genotype and rs146534657 AA genotype (5.63 ± 4.37) (p = 0.031).
  
  
  CONCLUSIONS
  Significantly lower A20 expression was found in RA patients. The polymorphisms of A20 were characterized in RA patients. We detected rs146534657 for the first time and identified a new A20 mutation (14284 T > A). A20 rs2230926 TG genotype and rs146534657 AG genotype may be related to poor outcome in RA patients.
authors.affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 125741799@qq.com.|Institute of Hematology, Jinan University, Guangzhou, 510632, China. 125741799@qq.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Oncology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 15857266@qq.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. 742630368@qq.com.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. 742630368@qq.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. 251582936@qq.com.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. 251582936@qq.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. lzw122623@aliyun.com.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. lingxu114@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 56085299@qq.com.
authors.forename: Huixia
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 41607951@qq.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 547932486@qq.com.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. jnyanglijian@163.com.
authors.forename: Lijian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. jnshaohuachen@163.com.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. jnlibo517@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. siulier@163.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. zhou21yi@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. yangqiuli@hotmail.com.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. yangqiuli@hotmail.com.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013582:Synovial Fluid / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3