Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease
Adult-onset Still’s disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To ass...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/8640719 |
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| author | Yi-Ming Chen Wei-Ting Hung Wan-Chun Chang Chia-Wei Hsieh Wen-Hung Chung Joung-Liang Lan Ning-Rong Gung Yun-Shien Lee Der-Yuan Chen Shuen-Iu Hung |
| author_facet | Yi-Ming Chen Wei-Ting Hung Wan-Chun Chang Chia-Wei Hsieh Wen-Hung Chung Joung-Liang Lan Ning-Rong Gung Yun-Shien Lee Der-Yuan Chen Shuen-Iu Hung |
| author_sort | Yi-Ming Chen |
| collection | DOAJ |
| description | Adult-onset Still’s disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5′-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P=1.20×10-8, OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n=82, median: 9.31 pg/mL), particularly in the cases with activity score≥6 (n=42, 10.94 pg/mL), compared to the healthy donors (n=68, 5.31 pg/mL) (P<0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P<0.0001) or AT genotype (11.61 pg/mL) (P=0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD. |
| format | Article |
| id | doaj-art-6d47a0e5198642a9bed14a4164960241 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-6d47a0e5198642a9bed14a41649602412025-02-03T01:26:57ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/86407198640719Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s DiseaseYi-Ming Chen0Wei-Ting Hung1Wan-Chun Chang2Chia-Wei Hsieh3Wen-Hung Chung4Joung-Liang Lan5Ning-Rong Gung6Yun-Shien Lee7Der-Yuan Chen8Shuen-Iu Hung9Division of Allergy, Immunology and Rheumatology, Department of Medical Research, Taichung Veterans General Hospital, 407 Taichung, TaiwanDivision of Allergy, Immunology and Rheumatology, Department of Medical Research, Taichung Veterans General Hospital, 407 Taichung, TaiwanDepartment of Dermatology, Drug Hypersensitivity Clinical and Research Center, Linkou Chang Gung Hospital, 333 Taoyuan, TaiwanDivision of Allergy, Immunology and Rheumatology, Department of Medical Research, Taichung Veterans General Hospital, 407 Taichung, TaiwanDepartment of Dermatology, Drug Hypersensitivity Clinical and Research Center, Linkou Chang Gung Hospital, 333 Taoyuan, TaiwanRheumatology and Immunology Center, China Medical University Hospital, 404 Taichung, TaiwanRheumatology and Immunology Center, China Medical University Hospital, 404 Taichung, TaiwanDepartment of Biotechnology, Ming Chuan University, 333 Taoyuan, TaiwanRheumatology and Immunology Center, China Medical University Hospital, 404 Taichung, TaiwanDepartment of Dermatology, Drug Hypersensitivity Clinical and Research Center, Linkou Chang Gung Hospital, 333 Taoyuan, TaiwanAdult-onset Still’s disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5′-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P=1.20×10-8, OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n=82, median: 9.31 pg/mL), particularly in the cases with activity score≥6 (n=42, 10.94 pg/mL), compared to the healthy donors (n=68, 5.31 pg/mL) (P<0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P<0.0001) or AT genotype (11.61 pg/mL) (P=0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD.http://dx.doi.org/10.1155/2020/8640719 |
| spellingShingle | Yi-Ming Chen Wei-Ting Hung Wan-Chun Chang Chia-Wei Hsieh Wen-Hung Chung Joung-Liang Lan Ning-Rong Gung Yun-Shien Lee Der-Yuan Chen Shuen-Iu Hung Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease Journal of Immunology Research |
| title | Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease |
| title_full | Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease |
| title_fullStr | Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease |
| title_full_unstemmed | Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease |
| title_short | Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease |
| title_sort | genetic association and expression correlation between colony stimulating factor 1 gene encoding m csf and adult onset still s disease |
| url | http://dx.doi.org/10.1155/2020/8640719 |
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