Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations
A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of te...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/7079359 |
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| author | Yuan-yuan Qi Xin-ran Liu Ying-xin He Min Zhou Xiang-hui Ning Ya-ling Zhai Xiao-xue Zhang Xiao-yang Wang Ya-fei Zhao Yan Cui Zhan-Zheng Zhao |
| author_facet | Yuan-yuan Qi Xin-ran Liu Ying-xin He Min Zhou Xiang-hui Ning Ya-ling Zhai Xiao-xue Zhang Xiao-yang Wang Ya-fei Zhao Yan Cui Zhan-Zheng Zhao |
| author_sort | Yuan-yuan Qi |
| collection | DOAJ |
| description | A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified (Pdiscovery=4.13×10−2, OR=0.58, 95% CI 0.35-0.98) and successfully replicated (Preplication=5.73×10−3, OR=0.45, 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations. |
| format | Article |
| id | doaj-art-7b143cb0d99e49a99cf6e6be056b39e6 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-7b143cb0d99e49a99cf6e6be056b39e62025-08-20T03:35:06ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/70793597079359Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese PopulationsYuan-yuan Qi0Xin-ran Liu1Ying-xin He2Min Zhou3Xiang-hui Ning4Ya-ling Zhai5Xiao-xue Zhang6Xiao-yang Wang7Ya-fei Zhao8Yan Cui9Zhan-Zheng Zhao10Nephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Ke Xue Avenue, Zhengzhou, Henan 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Ke Xue Avenue, Zhengzhou, Henan 450001, ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaNephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, ChinaA recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified (Pdiscovery=4.13×10−2, OR=0.58, 95% CI 0.35-0.98) and successfully replicated (Preplication=5.73×10−3, OR=0.45, 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.http://dx.doi.org/10.1155/2021/7079359 |
| spellingShingle | Yuan-yuan Qi Xin-ran Liu Ying-xin He Min Zhou Xiang-hui Ning Ya-ling Zhai Xiao-xue Zhang Xiao-yang Wang Ya-fei Zhao Yan Cui Zhan-Zheng Zhao Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations Journal of Immunology Research |
| title | Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations |
| title_full | Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations |
| title_fullStr | Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations |
| title_full_unstemmed | Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations |
| title_short | Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations |
| title_sort | association of the pinx1 variant rs6984094 which lengthens telomeres with systemic lupus erythematosus susceptibility in chinese populations |
| url | http://dx.doi.org/10.1155/2021/7079359 |
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