Genetics, Environment, and Gene-Environment Interactions in the Development of Systemic Rheumatic Diseases

Costenbader, Karen H.

doi:10.1016/j.rdc.2014.07.005

Cited by 79 publications

(52 citation statements)

References 134 publications

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“…For example, several studies Kremeyer et al 2005;Zawicki and Witas 2008) have screened skeletal samples for the presence of an allele (CCR5D32) that confers resistance to HIV in living populations and also might have been beneficial during medieval plague outbreaks. Other studies have explored the genetic basis of specific skeletal pathologies, including rheumatoid arthritis (Korczowska 2014), ankylosing spondylitis (Sparks and Costenbader 2014), periodontal disease (Genco and Borgnakke 2013;Kang et al 2014), osteochondritis dissecans (Bates et al 2014), bone cancers (Kuehl and Bergsagel 2002;Mundy 2002;Prideaux et al 2014), and hundreds of inherited skeletal disorders (Warman et al 2011).…”

Section: Examination Of Frailty and Demographymentioning

confidence: 99%

The Osteological Paradox 20 Years Later: Past Perspectives, Future Directions

2015

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More than 20 years ago, Wood et al. (Curr Anthropol 33:343-370, 1992) published ''The Osteological Paradox: Problems of Inferring Prehistoric Health from Skeletal Samples,'' in which they challenged bioarchaeologists to consider the effects of heterogeneous frailty and selective mortality on health inferences in past populations. Here, we review the paper's impact on bioarchaeology and paleopathology, focusing on recent advancements in studies of ancient health. We find the paper is often cited but infrequently engaged in a meaningful way. Despite an initial decade of limited progress, numerous researchers are now addressing components of the Paradox in more informed ways. We identify four areas of fruitful research: (1) intrasite, contextual perspectives, (2) subadults, (3) associating stress markers with demographic phenomena, and (4) skeletal lesion-formation processes. Although often seen as a problematic assumption, understanding the sources of heterogeneous frailty within human populations is a worthy research question in and of itself, and one that clearly links past and present health research within a global framework.

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Section: Examination Of Frailty and Demographymentioning

confidence: 99%

The Osteological Paradox 20 Years Later: Past Perspectives, Future Directions

2015

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“…Furthermore, recent studies have shown that fibrotic ILD is characterized by an increased distal alveolar bacterial burden that might be responsible for both a rapidly deteriorating course of fibrotic disease and deadly ‘exacerbations' [29]. The establishment via new DNA sequencing technologies of the long-time hypothetic theory that a disturbed lung microbiome could trigger and/or aggravate tissue injury in susceptible pulmonary fibrosis patients bears significant importance for CTD patients not only for its role in the development and maintenance of lung disease but also for its potential pathogenetic role in manifestations of the mater disease [62,63,64]. …”

Section: Acute Lung Infections In Ctdsmentioning

confidence: 99%

Acute Respiratory Events in Connective Tissue Disorders

Papiris¹,

Manali²,

Kolilekas³

et al. 2016

Respiration

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Subacute-acute, hyperacute, or even catastrophic and fulminant respiratory events occur in almost all classic connective tissue disorders (CTDs); they may share systemic life-threatening manifestations, may precipitously lead to respiratory failure requiring ventilatory support as well as a combination of specific therapeutic measures, and in most affected patients constitute the devastating end-of-life event. In CTDs, acute respiratory events may be related to any respiratory compartment including the airways, lung parenchyma, alveolar capillaries, lung vessels, pleura, and ventilatory muscles. Acute respiratory events may also precipitate disease-specific extrapulmonary organ involvement such as aspiration pneumonia and lead to digestive tract involvement and heart-related respiratory events. Finally, antirheumatic drug-related acute respiratory toxicity as well as lung infections related to the rheumatic disease and/or to immunosuppression complete the spectrum of acute respiratory events. Overall, in CTDs the lungs significantly contribute to morbidity and mortality, since they constitute a common site of disease involvement; a major site of infections related to the ‘mater' disease; a major site of drug-related toxicity, and a common site of treatment-related infectious complications. The extreme spectrum of the abovementioned events, as well as the ‘vicious' coexistence of most of the aforementioned manifestations, requires skills, specific diagnostic and therapeutic means, and most of all a multidisciplinary approach of adequately prepared and expert scientists. Avoiding lung disease might represent a major concern for future advancements in the treatment of autoimmune disorders.

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“…Taking RA as an example, there are now 101 identified genetic loci associated with RA. Strikingly, these currently identified loci account for less than half the genetic risk, with the HLA shared epitope accounting for 12% and the non-HLA loci accounting for an additional 5% of the total variance (23). The missing heritability is thought to arise from several factors, including epigenetic changes, gene-environment interactions, rare genetic variants, and common variants with effect sizes below current detection limits (24).…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types

Noss

Nguyen

Chang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14+ monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6–producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types.

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Genetics, Environment, and Gene-Environment Interactions in the Development of Systemic Rheumatic Diseases

Cited by 79 publications

References 134 publications

The Osteological Paradox 20 Years Later: Past Perspectives, Future Directions

The Osteological Paradox 20 Years Later: Past Perspectives, Future Directions

Acute Respiratory Events in Connective Tissue Disorders

Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types

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