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

Zhu L, Wang L, Wang X, Zhou L, Liao Z, Xu L, Wu H, Ren J, Li Z, Yang L, Chen S, Li B, Wu X, Zhou Y, Li Y - J Transl Med (2015)

Bottom Line: Significantly lower A20 mRNA expression was found in PBMCs from RA patients compared with healthy individuals (p < 0.001).Significantly lower A20 expression was found in RA patients.A20 rs2230926 TG genotype and rs146534657 AG genotype may be related to poor outcome in RA patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 125741799@qq.com.

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.

No MeSH data available.


Related in: MedlinePlus

Location of SNPs in the A20 gene locus.
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Fig1: Location of SNPs in the A20 gene locus.

Mentions: Most SNPs are located in intron 2 and 5, while two SNPs (rs146534657 and rs2230926) are located in exon 3 (Table 1; Figures 1, 2). However, the SNP frequencies appeared to be lower in the detected samples; the highest frequency was 24% (12/50 cases) for rs3799491 GA/AA genotype, and the lowest was 4.0% (2/50 case) for rs5029937 GT genotype, rs146534657 AG genotype, and without rs2307859 genotype respectively. In addition, the genotypes of four SNPs, rs2307859 (CCT deletion), rs661561 (homozygous), rs582757 (homozygous) and rs598493 (homozygous), appeared to be common genetic alterations in RA as they were identified in 41 cases, while the remaining 9 cases demonstrated different genotypic characteristics. However, 6 of the 8 SNPs were also identified in the healthy control group with similar frequency, and rs146534657 AG genotype and rs2307859 wild genotype were not identified in the healthy controls. However, there was no statistically significant difference in the proportion of genotypic data between the RA group and healthy group (Table 2). Moreover, genetic alterations in RA and healthy samples with the rs2230926 TG genotype and/or rs146534657 AG genotype were different from those lacking both SNPs (Table 3).Table 1


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

Zhu L, Wang L, Wang X, Zhou L, Liao Z, Xu L, Wu H, Ren J, Li Z, Yang L, Chen S, Li B, Wu X, Zhou Y, Li Y - J Transl Med (2015)

Location of SNPs in the A20 gene locus.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491428&req=5

Fig1: Location of SNPs in the A20 gene locus.
Mentions: Most SNPs are located in intron 2 and 5, while two SNPs (rs146534657 and rs2230926) are located in exon 3 (Table 1; Figures 1, 2). However, the SNP frequencies appeared to be lower in the detected samples; the highest frequency was 24% (12/50 cases) for rs3799491 GA/AA genotype, and the lowest was 4.0% (2/50 case) for rs5029937 GT genotype, rs146534657 AG genotype, and without rs2307859 genotype respectively. In addition, the genotypes of four SNPs, rs2307859 (CCT deletion), rs661561 (homozygous), rs582757 (homozygous) and rs598493 (homozygous), appeared to be common genetic alterations in RA as they were identified in 41 cases, while the remaining 9 cases demonstrated different genotypic characteristics. However, 6 of the 8 SNPs were also identified in the healthy control group with similar frequency, and rs146534657 AG genotype and rs2307859 wild genotype were not identified in the healthy controls. However, there was no statistically significant difference in the proportion of genotypic data between the RA group and healthy group (Table 2). Moreover, genetic alterations in RA and healthy samples with the rs2230926 TG genotype and/or rs146534657 AG genotype were different from those lacking both SNPs (Table 3).Table 1

Bottom Line: Significantly lower A20 mRNA expression was found in PBMCs from RA patients compared with healthy individuals (p < 0.001).Significantly lower A20 expression was found in RA patients.A20 rs2230926 TG genotype and rs146534657 AG genotype may be related to poor outcome in RA patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. 125741799@qq.com.

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.

No MeSH data available.


Related in: MedlinePlus