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Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation.

ABSTRACT: In this review, we explore systemization of knowledge about the triggering effects of non-genetic factors in pathogenic mechanisms that contribute to the development of rheumatoid arthritis (RA). Possible mechanisms involving environmental and individual factors in RA pathogenesis were analyzed, namely, infections, mental stress, sleep deprivation ecology, age, perinatal and gender factors, eating habits, obesity and smoking. The non-genetic factors modulate basic processes in the body with the impact of these factors being non-specific, but these common challenges may be decisive for advancement of the disease in the predisposed body at risk for RA. The provocation of this particular disease is associated with the presence of congenital loci minoris resistentia. The more frequent non-genetic factors form tangles of interdependent relationships and, thereby, several interdependent external factors hit one vulnerable basic process at once, either provoking or reinforcing each other. Understanding the specific mechanisms by which environmental and individual factors impact an individual under RA risk in the preclinical stages can contribute to early disease diagnosis and, if the factor is modifiable, might be useful for the prevention or delay of its development.

SUBMITTER: Arleevskaya M

PROVIDER: S-EPMC9329780 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation.

Arleevskaya Marina M Takha Elena E Petrov Sergey S Kazarian Gevorg G Renaudineau Yves Y Brooks Wesley W Larionova Regina R Korovina Marina M Valeeva Anna A Shuralev Eduard E Mukminov Malik M Kravtsova Olga O Novikov Andrey A

International journal of molecular sciences 20220723 15

In this review, we explore systemization of knowledge about the triggering effects of non-genetic factors in pathogenic mechanisms that contribute to the development of rheumatoid arthritis (RA). Possible mechanisms involving environmental and individual factors in RA pathogenesis were analyzed, namely, infections, mental stress, sleep deprivation ecology, age, perinatal and gender factors, eating habits, obesity and smoking. The non-genetic factors modulate basic processes in the body with the ...[more]

PMID: 35897715

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Project description:ObjectiveTo evaluate the influence of lifestyle, reproduction, and some external factors on the development of rheumatoid arthritis (RA) and to describe its comorbidity.MethodsCases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected population referents. Data on possible aetiological factors and comorbidity were collected by postal questionnaire.ResultsThe response rates were 67% among cases and 59% among referents. A decrease in the occurrence of atopic allergy was seen in the cases (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4 to 1.0). There was a positive association between RA and insulin treatment (OR 10.2, 95% CI 1.7 to 60.8) in women, and women with a short fertile period had an increased risk of RA (OR 2.5, 95% CI 1.1 to 5.4). Current and previous smoking were associated with increased risks for RA in both sexes, and in men a dose-response relationship was found with number of tobacco pack years (p for trend <0.005). The risk for RA decreased with increasing level of education in both men and women. Increased risks were seen in men born into households with private wells (OR 2.8, 95% CI 1.5 to 5.2), residentially exposed to mould (OR 4.6, 95% CI 1.1 to 20.2), or exposed to farm animals (OR 3.3, 95% CI 0.7 to 16.6). In women there were positive associations between RA and reporting a previous joint injury (OR 2.5, 95% CI 1.0 to 6.6) and prolonged exposure to hair dyes (OR 1.9, 95% CI 0.8 to 4.5).ConclusionsRA, a disease with features of T helper 1 (Th1) dominated immune response, was inversely associated with atopic allergy, a Th2 dominated condition, while there were indications of a strong positive association with Th1 related diabetes mellitus. The results support a causal relationship between smoking and RA. The level of education was inversely associated with RA, while there was a positive association between RA and certain residential factors in men and a short fertile period in women.

Project description:Rheumatoid arthritis (RA) is a multifactorial chronic autoimmune disease, which involves a complex interplay of environmental triggers and genetic components in its etiology. It has been shown that genetics only explain about half of the liability to develop RA, leaving a large room for non-genetic factors. Indeed, several environmental exposures including smoking, drinking, obesity, and dietary patterns (and more) have been identified to be associated with RA risk, yet the observational nature of conventional epidemiological investigation hampers causal inference, as the validity of results could be plagued by measurement error, confounding, and/or reverse causality. Mendelian randomization (MR) is a novel statistical approach that uses genetic variants as instrumental variables (IV) to make causal inferences from observational data. The current genetic discoveries in the many heritable and modifiable human complex traits have provided an exceptional opportunity to evaluate a putative causal relationship between exposure and outcome in the absence of high-quality experimental or intervention studies, through a MR design. In the current review, we detail the contribution of MR studies hitherto conducted for modifiable environmental exposures with the risk of RA to understand the role of these factors in RA pathogenesis. We start with a brief introduction of each study, follow by a summarization of shortcomings and conclude by highlighting future directions. The application of MR design in the field of rheumatology remains limited. Only a few MR studies have examined the causal roles of vitamin D, cigarette smoking, alcohol consumption, coffee consumption, and levels of education in RA, where, no consistent evidence for a causal relationship has been found. Most studies lacked sensitivity analyses to verify MR model assumptions and to guarantee the validity of results. Almost all studies are likely to bias the strength of association towards a null value, since they used IVs from earlier GWAS(s) of exposures with a small sample size (i.e., few genetic markers). As the magnitudes of GWAS expand rapidly, additional trait-associated loci have been discovered. Incorporating these loci would greatly improve the strength of genetic instruments, as well as both the accuracy and precision of MR estimates. To conclude, there is a need for an update and a huge space for improvement of future MR studies in RA.

Dataset Information

Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation.

Publications

Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation.

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