The Genetics of Scleroderma

Martín, Javier; Fonseca, Carmen

doi:10.1007/s11926-010-0139-5

Cited by 20 publications

(19 citation statements)

References 44 publications

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“…SSc is a complex disease, where no single polymorphism is known to cause the complete manifestation of the condition; it has been suggested that it may be the combined action of several single nucleotide polymorphisms in different genes that may result in the complex traits of the disease. 7 We compared patients with SSc with a control population and demonstrated that oral problems in patients with SSc include decreased oral opening, decreased saliva production, increased number of missing teeth, and worse periodontal disease. [8][9][10] The radiographic manifestations in the jaws, considered characteristic of SSc, are welldefined bony erosions at the sites of muscle attachment in the mandible and increasing width of periodontal ligaments around teeth.…”

mentioning

confidence: 99%

The Canadian Systemic Sclerosis Oral Health Study IV: oral radiographic manifestations in systemic sclerosis compared with the general population

Dagenais

MacDonald

Baron

et al. 2015

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Objective-The aim of this study was to compare oral radiologic abnormalities associated with systemic sclerosis (SSc) against abnormalities in the general population.Study Design-Patients with SSc and healthy controls were enrolled in a multi-site crosssectional study. Included in the radiology examination were a panoramic radiograph, four bitewings, and an anterior mandibular periapical radiograph. Radiographs were evaluated by two oral and maxillofacial radiologists tested for interobserver and intraobserver reliability. Chisquared tests, Fisher exact tests, and Mann Whitney U tests were used to summarize the radiologic manifestations of patients and controls.Results-We assessed 163 SSc patients and 231 controls. Widening of the periodontal ligament space (PLS) (P < .001), with higher percentage of teeth with PLS widening (P < .001), was significantly more frequent in patients with SSc than in controls. The most significant differences between the two groups were found in the molars and premolars (P < .001). Moreover, 26% of the patients with SSc had a periapical PLS greater than 0.19 mm compared with 13% of the controls (P = .003). Patients with SSc had significantly more erosions compared with controls (14.5% vs. 3.6%; P < .001), mostly in the condyles (P = .022), coronoid processes (P = .005) and other locations (P = .012). CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptConclusion-Patients with SSc had more teeth with PLS widening and erosions of the mandible compared with controls.Systemic sclerosis (SSc) is a multi-system disorder of connective tissue characterized clinically by thickening and fibrosis of the skin and involvement of internal organs. Prevalence estimates for SSc are between 240 per million 1 and 276 per million 2 in an American population. The incidence rate of SSc is about 20 new cases per million per year. 3 It affects mainly women in their third or fourth decade of life and is associated with significant morbidity and increased mortality. No treatment has been shown to alter the natural history of SSc. 4 SSc is characterized by fibroblast dysfunction, which leads to fibrosis of the skin, internal organs, or both; 5 autoantibodies (anticentromere, antitopoisomerase I, anti-RNA polymerase III); and vasculopathy. 5,6 SSc is usually categorized into limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc without skin involvement. 6 Although several candidate genes and regions of the genome have been identified as potentially being involved in SSc, these are also associated with other autoimmune conditions. SSc is a complex disease, where no single polymorphism is known to cause the complete manifestation of the condition; it has been suggested that it may be the combined action of several single nucleotide polymorphisms in different genes that may result in the complex traits of the disease. 7 We compared patients with SSc with a control population and demonstrated that oral problems in patients with SSc include decreased oral opening, decreased s...

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mentioning

confidence: 99%

The Canadian Systemic Sclerosis Oral Health Study IV: oral radiographic manifestations in systemic sclerosis compared with the general population

Dagenais

MacDonald

Baron

et al. 2015

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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“…6 The fact that the IL2RA rs11594656 minor allele shows a protective effect in both SLE 6 and SSc (the current study) should also be noted, because these diseases have a very similar genetic component and most of their shared associations are in the same direction. 9,10 Moreover, low circulating levels of soluble IL2RA have been found to be associated with the IL2RA Table 2 Pooled analysis of the allelic combinations of the IL2RA genomic region accordingly with the global disease (SSc), the limited subtype (lcSSc) and ACA production Allelic combination Controls, Abbreviations: ACA, anti-centromere auto-antibodies; CI, confidence interval; OR, odds ratio.…”

Section: Discussionmentioning

confidence: 99%

“…For example, most of the genetic associations of systemic sclerosis (SSc) are shared with SLE. 9,10 SSc, also called scleroderma, is a chronic multisystem disease of unknown aetiology, characterised by fibrotic events, vasculopathy and production of auto-antibodies against nuclear self-antigens, including anti-centromere auto-antibodies (ACAs) and anti-topoisomerase antibodies (ATA). 11 Two main clinical subsets of the disease have been described based on the extent of skin involvement: limited cutaneous scleroderma (lcSSc) and diffuse cutaneous scleroderma (dcSSc).…”

Section: Introductionmentioning

confidence: 99%

The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis

et al. 2011

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Regulatory T cells (T regs ) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor a (IL2RA) is an important T reg marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P FDR ¼ 2.07 Â 10 À4 , odds ratio ¼ 1.30 (1.14 -1.47)). The associations of rs11594656 and rs12722495 were lost

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“…Studies on genetic susceptibility suggest that HLA/MHC-associated loci and other non-associated loci are involved in the pathogenesis of SSc (20) . The HLA-associated gene NOTCH4 has been linked to both SSc-specific antibodies: antitopoisomerase-I antibody (ATA) and anti-centromere antibody (ACA).…”

Section: Overview Of Systemic Sclerosismentioning

confidence: 99%