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Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients
OBJECTIVES: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort. PATIENTS AND METHODS: This retrospective study was conducted between January 2001 and December...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Turkish League Against Rheumatism
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957766/ https://www.ncbi.nlm.nih.gov/pubmed/35382366 http://dx.doi.org/10.46497/ArchRheumatol.2021.8127 |
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author | Pang Leong, Khai Yun Yong, Mei Ling Goh, Liuh Mun Woo, Chia Wei Lim, Chia Koh, Ee Tzun |
author_facet | Pang Leong, Khai Yun Yong, Mei Ling Goh, Liuh Mun Woo, Chia Wei Lim, Chia Koh, Ee Tzun |
author_sort | Pang Leong, Khai |
collection | PubMed |
description | OBJECTIVES: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort. PATIENTS AND METHODS: This retrospective study was conducted between January 2001 and December 2017. We selected Chinese RA patients positive for anti-citrullinated peptide antibody (ACPA). All the 128 known candidate genes identified through genome-wide association studies were sequenced in 48 RA patients (15 males, 33 females; mean age 53.32±8.98 years; range, 32 to 75 years) and 45 controls (11 males, 34 females; mean age 32.18±9.54; range, 21 to 57 years). The exonic regions of these genes were sequenced. The resultant data were analyzed for association using single variant association and pathway-based association enrichment tests. The genetic burden due to low-frequency variants was assessed with the C-alpha test. The candidate variants that showed significant association were validated in a larger cohort of 500 RA cases (71 males, 429 females; mean age 48.6±12.2 years; range, 24 to 92 years) and 500 controls (66 males, 434 females; mean age 32.3±10.1 years; range, 21 to 73 years). RESULTS: Thirty-nine variants in 21 genes were identified using single variant association analysis and C-alpha test, with stepwise filtering. Among these, the missense variant in interleukin-6 signal transducer (IL-6ST) 5:55260065 (p.Cys47Phe) was significantly associated with RA in Chinese patients in Singapore. CONCLUSION: Our results suggest that a mutation in IL-6ST (5:55260065) confers risk of RA in Chinese patients in Singapore. |
format | Online Article Text |
id | pubmed-8957766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Turkish League Against Rheumatism |
record_format | MEDLINE/PubMed |
spelling | pubmed-89577662022-04-04 Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients Pang Leong, Khai Yun Yong, Mei Ling Goh, Liuh Mun Woo, Chia Wei Lim, Chia Koh, Ee Tzun Arch Rheumatol Original Article OBJECTIVES: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort. PATIENTS AND METHODS: This retrospective study was conducted between January 2001 and December 2017. We selected Chinese RA patients positive for anti-citrullinated peptide antibody (ACPA). All the 128 known candidate genes identified through genome-wide association studies were sequenced in 48 RA patients (15 males, 33 females; mean age 53.32±8.98 years; range, 32 to 75 years) and 45 controls (11 males, 34 females; mean age 32.18±9.54; range, 21 to 57 years). The exonic regions of these genes were sequenced. The resultant data were analyzed for association using single variant association and pathway-based association enrichment tests. The genetic burden due to low-frequency variants was assessed with the C-alpha test. The candidate variants that showed significant association were validated in a larger cohort of 500 RA cases (71 males, 429 females; mean age 48.6±12.2 years; range, 24 to 92 years) and 500 controls (66 males, 434 females; mean age 32.3±10.1 years; range, 21 to 73 years). RESULTS: Thirty-nine variants in 21 genes were identified using single variant association analysis and C-alpha test, with stepwise filtering. Among these, the missense variant in interleukin-6 signal transducer (IL-6ST) 5:55260065 (p.Cys47Phe) was significantly associated with RA in Chinese patients in Singapore. CONCLUSION: Our results suggest that a mutation in IL-6ST (5:55260065) confers risk of RA in Chinese patients in Singapore. Turkish League Against Rheumatism 2021-11-03 /pmc/articles/PMC8957766/ /pubmed/35382366 http://dx.doi.org/10.46497/ArchRheumatol.2021.8127 Text en Copyright © 2021, Turkish League Against Rheumatism https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Article Pang Leong, Khai Yun Yong, Mei Ling Goh, Liuh Mun Woo, Chia Wei Lim, Chia Koh, Ee Tzun Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients |
title | Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients |
title_full | Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients |
title_fullStr | Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients |
title_full_unstemmed | Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients |
title_short | Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients |
title_sort | missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in chinese patients |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957766/ https://www.ncbi.nlm.nih.gov/pubmed/35382366 http://dx.doi.org/10.46497/ArchRheumatol.2021.8127 |
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