DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis
Abstract Background Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-03-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-017-1276-2 |
| _version_ | 1819028384199475200 |
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| author | Weida Meng Zaihua Zhu Xia Jiang Chun Lai Too Steffen Uebe Maja Jagodic Ingrid Kockum Shahnaz Murad Luigi Ferrucci Lars Alfredsson Hejian Zou Lars Klareskog Andrew P. Feinberg Tomas J. Ekström Leonid Padyukov Yun Liu |
| author_facet | Weida Meng Zaihua Zhu Xia Jiang Chun Lai Too Steffen Uebe Maja Jagodic Ingrid Kockum Shahnaz Murad Luigi Ferrucci Lars Alfredsson Hejian Zou Lars Klareskog Andrew P. Feinberg Tomas J. Ekström Leonid Padyukov Yun Liu |
| author_sort | Weida Meng |
| collection | DOAJ |
| description | Abstract Background Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA. Methods We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA. Results We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723. Conclusions We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors. |
| first_indexed | 2024-12-21T05:57:30Z |
| format | Article |
| id | doaj.art-ddcecb34baf74482870b8d9eb514cea1 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-21T05:57:30Z |
| publishDate | 2017-03-01 |
| publisher | BMC |
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| series | Arthritis Research & Therapy |
| spelling | doaj.art-ddcecb34baf74482870b8d9eb514cea12022-12-21T19:13:50ZengBMCArthritis Research & Therapy1478-63622017-03-0119111010.1186/s13075-017-1276-2DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritisWeida Meng0Zaihua Zhu1Xia Jiang2Chun Lai Too3Steffen Uebe4Maja Jagodic5Ingrid Kockum6Shahnaz Murad7Luigi Ferrucci8Lars Alfredsson9Hejian Zou10Lars Klareskog11Andrew P. Feinberg12Tomas J. Ekström13Leonid Padyukov14Yun Liu15Department of Biochemistry and Molecular Biology, The Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, School of Basic Medical Sciences, Fudan UniversityDivision of Rheumatology, Huashan Hospital, Fudan UniversityInstitute of Environmental Medicine, Karolinska InstitutetInstitute for Medical Research, Jalan PahangInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska InstitutetDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska InstitutetInstitute for Medical Research, Jalan PahangInstramural Research Program, National Institute on Aging, National Institutes of HealthInstitute of Environmental Medicine, Karolinska InstitutetDivision of Rheumatology, Huashan Hospital, Fudan UniversityRheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University HospitalCenter for Epigenetics and Departments of Medicine, Johns Hopkins University School of MedicineDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska InstitutetRheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University HospitalDepartment of Biochemistry and Molecular Biology, The Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, School of Basic Medical Sciences, Fudan UniversityAbstract Background Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA. Methods We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA. Results We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723. Conclusions We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.http://link.springer.com/article/10.1186/s13075-017-1276-2Rheumatoid arthritisSmokingEpidemiology |
| spellingShingle | Weida Meng Zaihua Zhu Xia Jiang Chun Lai Too Steffen Uebe Maja Jagodic Ingrid Kockum Shahnaz Murad Luigi Ferrucci Lars Alfredsson Hejian Zou Lars Klareskog Andrew P. Feinberg Tomas J. Ekström Leonid Padyukov Yun Liu DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis Arthritis Research & Therapy Rheumatoid arthritis Smoking Epidemiology |
| title | DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis |
| title_full | DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis |
| title_fullStr | DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis |
| title_full_unstemmed | DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis |
| title_short | DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis |
| title_sort | dna methylation mediates genotype and smoking interaction in the development of anti citrullinated peptide antibody positive rheumatoid arthritis |
| topic | Rheumatoid arthritis Smoking Epidemiology |
| url | http://link.springer.com/article/10.1186/s13075-017-1276-2 |
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