PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations
BackgroundSystemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease that is characterized by the production of autoantibodies. Although accumulated evidence suggests that the dysregulation of long non-coding RNAs (lncRNAs) is involved in the pathogenesis of SLE, the genetic con...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.987385/full |
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| author | Xiao-Xue Zhang Jun-Peng You Xin-Ran Liu Ya-Fei Zhao Yan Cui Yan Cui Zhan-Zheng Zhao Yuan-Yuan Qi |
| author_facet | Xiao-Xue Zhang Jun-Peng You Xin-Ran Liu Ya-Fei Zhao Yan Cui Yan Cui Zhan-Zheng Zhao Yuan-Yuan Qi |
| author_sort | Xiao-Xue Zhang |
| collection | DOAJ |
| description | BackgroundSystemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease that is characterized by the production of autoantibodies. Although accumulated evidence suggests that the dysregulation of long non-coding RNAs (lncRNAs) is involved in the pathogenesis of SLE, the genetic contributions of lncRNA coding genes to SLE susceptibility remain largely unknown. Here, we aimed to provide more evidence for the role of lncRNA coding genes to SLE susceptibility.MethodsThe genetic association analysis was first adopted from the previous genome-wide association studies (GWAS) and was then validated in an independent cohort. PRDX6-AS1 is located at chr1:173204199-173446294. It spans a region of approximately 240 kb, and 297 single nucleotide polymorphisms (SNPs) were covered by the previous GWAS. Differential expression at the mRNA level was analyzed based on the ArrayExpress Archive database.ResultsA total of 33 SNPs were associated with SLE susceptibility, with a P<1.68×10-4. The strongest association signal was detected at rs844649 (P=2.12×10-6), according to the previous GWAS. Combining the results from the GWAS Chinese cohort and our replication cohort, we pursued a meta-analysis approach and found a pronounced genetic association between PRDX6-AS1 rs844649 and SLE susceptibility (pmeta=1.24×10-13, OR 1.50, 95% CI: 1.34–1.67). The mRNA expression of PRDX6 was elevated in peripheral blood cells, peripheral blood mononuclear cells (PBMCs), and multiple cell subpopulations, such as B cells, CD4+ T cells, CD3+ cells, and monocytes in patients with SLE. The PRDX6 protein expression level was also increased in patients with SLE compared with healthy donors.ConclusionOur study provides new evidence that variants located in lncRNA coding genes are associated with SLE susceptibility. |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T17:21:03Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-1f0f62969d6c435f8a854ef6aa30cfcc2022-12-22T04:12:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.987385987385PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populationsXiao-Xue Zhang0Jun-Peng You1Xin-Ran Liu2Ya-Fei Zhao3Yan Cui4Yan Cui5Zhan-Zheng Zhao6Yuan-Yuan Qi7Nephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaBackgroundSystemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease that is characterized by the production of autoantibodies. Although accumulated evidence suggests that the dysregulation of long non-coding RNAs (lncRNAs) is involved in the pathogenesis of SLE, the genetic contributions of lncRNA coding genes to SLE susceptibility remain largely unknown. Here, we aimed to provide more evidence for the role of lncRNA coding genes to SLE susceptibility.MethodsThe genetic association analysis was first adopted from the previous genome-wide association studies (GWAS) and was then validated in an independent cohort. PRDX6-AS1 is located at chr1:173204199-173446294. It spans a region of approximately 240 kb, and 297 single nucleotide polymorphisms (SNPs) were covered by the previous GWAS. Differential expression at the mRNA level was analyzed based on the ArrayExpress Archive database.ResultsA total of 33 SNPs were associated with SLE susceptibility, with a P<1.68×10-4. The strongest association signal was detected at rs844649 (P=2.12×10-6), according to the previous GWAS. Combining the results from the GWAS Chinese cohort and our replication cohort, we pursued a meta-analysis approach and found a pronounced genetic association between PRDX6-AS1 rs844649 and SLE susceptibility (pmeta=1.24×10-13, OR 1.50, 95% CI: 1.34–1.67). The mRNA expression of PRDX6 was elevated in peripheral blood cells, peripheral blood mononuclear cells (PBMCs), and multiple cell subpopulations, such as B cells, CD4+ T cells, CD3+ cells, and monocytes in patients with SLE. The PRDX6 protein expression level was also increased in patients with SLE compared with healthy donors.ConclusionOur study provides new evidence that variants located in lncRNA coding genes are associated with SLE susceptibility.https://www.frontiersin.org/articles/10.3389/fimmu.2022.987385/fullsystemic lupus erythematosussingle nucleotide polymorphismsPRDX6-AS1lncRNArs844649 |
| spellingShingle | Xiao-Xue Zhang Jun-Peng You Xin-Ran Liu Ya-Fei Zhao Yan Cui Yan Cui Zhan-Zheng Zhao Yuan-Yuan Qi PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations Frontiers in Immunology systemic lupus erythematosus single nucleotide polymorphisms PRDX6-AS1 lncRNA rs844649 |
| title | PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations |
| title_full | PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations |
| title_fullStr | PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations |
| title_full_unstemmed | PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations |
| title_short | PRDX6AS1 gene polymorphisms and SLE susceptibility in Chinese populations |
| title_sort | prdx6as1 gene polymorphisms and sle susceptibility in chinese populations |
| topic | systemic lupus erythematosus single nucleotide polymorphisms PRDX6-AS1 lncRNA rs844649 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.987385/full |
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