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. 2015 Jul 5:13:215.
doi: 10.1186/s12967-015-0566-1.

Characteristics of A20 gene polymorphisms and clinical significance in patients with rheumatoid arthritis

Lihua Zhu  1   2 , Liang Wang  3 , Xu Wang  4   5 , Lingling Zhou  6   7 , Ziwei Liao  8 , Ling Xu  9 , Huixia Wu  10 , Jie Ren  11 , Zhaoxia Li  12 , Lijian Yang  13 , Shaohua Chen  14 , Bo Li  15 , Xiuli Wu  16 , Yi Zhou  17 , Yangqiu Li  18   19
Affiliations

Characteristics of A20 gene polymorphisms and clinical significance in patients with rheumatoid arthritis

Lihua Zhu et al. J Transl Med. .

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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Location of SNPs in the A20 gene locus.
Figure 2
Figure 2
Identification of A20 SNPs in RA patients. Arrows indicate sites of nucleotide changes. Wild wild-type, Homo homozygous, Heter heterozygous.
Figure 3
Figure 3
New mutation identified in A20 in synovial fluid from a patient with RA. Arrows indicate sites of nucleotide changes. Wild wild-type, Heter heterozygous.
Figure 4
Figure 4
A20 expression level in RA patients and healthy individuals (HI).
Figure 5
Figure 5
Comparison of A20 expression level between SNPs (RA patients with rs2230926 TG genotype and rs146534657 AG genotype) and WT (RA patients with rs2230926 TT genotype and rs146534657 AA genotype).
Figure 6
Figure 6
Comparison of the A20 expression level between samples with rs3799491 or rs661561 SNPs. a A20 expression level in patients with rs3799491 AA/GA genotypes and with rs3799491 GG genotype. b A20 expression level in patients with rs661561 AA/AC genotypes (heterozygous) and with rs661561 CC genotype (homozygous).
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