DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis

Meng W, Zhu Z, Jiang X, Too CL, Uebe S, Jagodic M, Kockum I, Murad S, Ferrucci L, Alfredsson L, Zou H, Klareskog L, Feinberg AP, Ekstrom TJ, Padyukov L, Liu Y (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Arthritis Research & Therapy BioMed Central

Book Volume: 19

Pages Range: 71

Journal Issue: 1

DOI: 10.1186/s13075-017-1276-2

Abstract

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.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.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.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.

Authors with CRIS profile

Steffen Uebe Institute of Human Genetics

Involved external institutions

Fudan University / 复旦大学 CN China (CN) Karolinska Institute SE Sweden (SE) Johns Hopkins University (JHU) US United States (USA) (US) National Institute on Aging (NIA) US United States (USA) (US) Institute for Medical Research (IMR) MY Malaysia (MY)

How to cite

APA:

Meng, W., Zhu, Z., Jiang, X., Too, C.L., Uebe, S., Jagodic, M.,... Liu, Y. (2017). DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis. Arthritis Research & Therapy, 19(1), 71. https://doi.org/10.1186/s13075-017-1276-2

MLA:

Meng, Weida, et al. "DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis." Arthritis Research & Therapy 19.1 (2017): 71.

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