Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case–control study

Yahya, Abqariyah; Bengtsson, Camilla; Lai, Too Chun; Larsson, Per; Mustafa, Amal Nasir; Abdullah, Nor Aini; Muhamad, Norasiah; Heselynn, H.; Klareskog, Lars; Alfredsson, Lars; Murad, Shahnaz

doi:10.3109/s10165-011-0544-2

Cited by 30 publications

(20 citation statements)

References 16 publications

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“…Of the 10 studies that met the predefined inclusion criteria, 4 were from North America [4,14,16,20], 5 from Europe [2,5,21,22,24], and 1 from Malaysia [23], and they included a total of 181 100 subjects and 4,552 RA cases (Table 1). The median of the highest category of number of pack-years analyzed in each study ranged between 15 and more than 55 pack-years, while the reference group for all studies was never smokers.…”

Section: Resultsmentioning

confidence: 99%

Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

et al. 2014

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IntroductionAlthough previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA.MethodsRelevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis.ResultsWe included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies.ConclusionsLifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years.

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Section: Resultsmentioning

confidence: 99%

Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

et al. 2014

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“…Malays, Chinese, and Indians). The details of the MyEIRA study have been described elsewhere [3, 17]. In brief, patients with early RA were identified from nine rheumatology centers throughout Peninsular Malaysia, and for each case, a population control was randomly selected matched by age, sex, and residential area.…”

Section: Methodsmentioning

confidence: 99%

“…One example of this is the shared epitope (SE) alleles of the human leukocyte antigen DR beta chain 1 (HLA-DRB1), which is a major risk factor for ACPA-positive RA, but not to the same extent for ACPA-negative RA. Environmental/lifestyle factors, such as smoking [1–3] and other noxious airway exposures [4, 5], have been shown to be risk factors for RA, mainly for the ACPA-positive subset of RA.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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BackgroundMultiple 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.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1276-2) contains supplementary material, which is available to authorized users.

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“…In early RA patients, smoking was associated with higher RA disease activity (number of tender joints, Larsen's score, DAS-28, higher frequency of autoantibodies), and severity independent of age, alcohol consumption, follow-up duration, and gender [23,24,30]. Prospective monitoring of 100 early RA patients for 2 years indicated that RA disease activity (swollen and tender joints, pain) increased stepwise from never smokers to former smokers to current smokers [31].…”

Section: Smoking's Effect On Ra Diseasementioning

confidence: 99%

“…Longer duration and higher intensity of smoking increased the risk of onset of RA [22], especially ACPA positive RA [23]. Smoking was associated with earlier age of onset of RA [24,25].…”

Section: Smoking's Effect On Ra Diseasementioning

confidence: 99%

Effects of Smoking on Immunologic and Skeletal Mechanisms Involved in Rheumatoid Arthritis and Responses of Various Biologic Therapies for RA

Molnar-Kimber¹

2013

J Clin Cell Immunol

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Smoking is considered a major risk factor in the onset of rheumatoid arthritis. Smokers who also carry the HLA-DR4 shared epitope have a higher risk of development of RA. Smoking releases more than 4000 compounds which not only affect the cardiovascular and respiratory systems but also bone and joint health. Smokers have a higher risk for bone fractures, development of osteoporosis, and degeneration of intervertebral discs. Bone fractures of most smokers heal slower than those of most controls. Smoking also lowers bone mineral density, increases production of proinflammatory cytokines, and augments the risk of citrullination of proteins in the lungs, and possibly in the joints. RA patients who generated antibodies to cyclic citrullinated proteins (CCP) have a higher risk for joint erosions. Although response rates are significantly higher in nonsmoking early RA patients than nonsmoking RA patients with long-standing disease, response rates are not significantly improved in smoking early RA patients. Smoking has decreased response rates to TNF blockers. Additional studies indicated that smoking significantly reduced the response rate of infliximab but not etanercept or adalimumab in RA patients. Because one TNF blocker (infliximab) had significantly lower response rates in a subpopulation of RA patients (smokers versus never smokers) than two distinct TNF blockers, criteria for the development and approval of biosimilars may need to include in vivo trials as well as a demonstration of activity against the primary target (e.g. TNFα). Although the most straight forward recommendation is for patients to stop smoking, investigations on the effect of smoking on response to therapies may serve as a model for elucidating the effect of other environmental contaminants such as air pollution on the response to treatment of flares in RA patients.

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Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case–control study

Cited by 30 publications

References 16 publications

Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

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

Effects of Smoking on Immunologic and Skeletal Mechanisms Involved in Rheumatoid Arthritis and Responses of Various Biologic Therapies for RA

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