| Causes of Scleroderma (MAIN MENU) |
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| Causes of Scleroderma: Genetics |
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| Overview |
| Genetics and proteomics in scleroderma. Genetic, familial, and twin studies suggest that SSc occurs in genetically susceptible individuals. Recent high-throughput technologies, including gene expression profiling and proteomics, have accelerated the rate of information acquired on possible mechanisms involved in SSc pathogenesis. PubMed. Curr Rheumatol Rep. 2005 Apr;7(2):129-34. |
 Scleroderma Care and Research Journal (PDF) This journal for physicians focuses on elevating the standards of care for digital ischemia in scleroderma. Articles include The Genetics of Scleroderma: What Every Rheumatologist Should Know, as well as Digital Ulceration and Critical Digital Ischemia in Scleroderma. Journal of the Scleroderma Clinical Trials Consortium (SCTC) Vol 1, No. 2, Winter 2003. (Also see: Scleroderma DNA and Family Registry) |
| Gene profiling of scleroderma skin reveals robust signatures of disease that are imperfectly reflected in the transcript profiles of explanted fibroblasts. SSc has a distinct gene profile that is not confounded by geographic location, indicating that extended multicenter studies may be worthwhile to identify distinct subsets of disease by transcript profiling. PubMed. Arthritis Rheum. 2006 Jun;54(6):1961-73. |
| Target identification and validation in systemic autoimmunity. Recent genome-based approaches to autoimmunity, have revealed novel pathogenic targets, including genes that negatively regulate T- and/or B-cell effector differentiation, as well as genes that specifically regulate T- cell-B-cell collaboration. It is hoped that continued investigation of such pathogenic targets will yield novel and specific therapeutic agents for the treatment of human autoimmune conditions. PubMed. Immunol Res. 2005;32(1-3):201-10. (Also see: Causes of Scleroderma: T Cells) |
| Paths to understanding the genetic basis of autoimmune disease. Marked advances in genetic resources and tools are now making it possible to identify the sequence variants that contribute to autoimmune diseases—promising a better understanding of how we normally remain tolerant of our own tissue components, and how this goes wrong in autoimmune disease. PubMed. Nature. 2005 Jun 2;435(7042):584-9. |
| An array of possibilities for the study of autoimmunity. Genomic and proteomic technologies are already providing useful information about autoimmune disease, and they are likely to lead to important discoveries within the next decade. PubMed. Nature. 2005 Jun 2;435(7042):605-11. |
| Swedish team find gene with link to major diseases. Scientists have identified a gene which links autoimmune diseases with cardiovascular diseases. The gene variant when it is present in the body, leads to a reduction in the production of a number of immune defence proteins. News-Medical.Net 04/12/05. (Also see: Cardiac Research) |
| Genetic studies in the rheumatic diseases: present status and implications for the future. Newer techniques being developed presently, such as high density single nucleotide polymorphism genome-wide scanning, show promise to bring these analyses to the next level, which will hopefully result not only in better screening of individuals at highest risk, but also in novel treatments. PubMed. J Rheumatol Suppl. 2005 Jan;72:10-3. |
| Genetic insights into disease mechanisms of autoimmunity. These data suggest that both general and disease-specific mechanisms lead to the clinical outcome of autoimmune disease and that increased understanding of these mechanisms will improve our knowledge of how autoimmune disease occurs, eventually leading to the development of novel therapeutic agents. PubMed. Br Med Bull. 2005 Feb 08;71:93-113. |
| Candidate Genes Associated with Systemic Sclerosis (SSc): A Family-Based Genetic Association Study Using 116 SNPs. SPARC, FBN1, and TOP1 have been implicated as important in SSc in other studies. SLC22A4 has been associated with rheumatoid arthritis, and this gene as well as SLC9A3R1, and raptor have been associated with susceptibility to psoriasis. This is the largest genetic association study ever reported in systemic sclerosis. These data obtained from a general SSc population, confirm genetic associations previously reported in the Choctaw and our previous SSc family study and identify additional genetic associations not previously reported in this disease. Maureen D. Mayes. 1653/475. ACR 2004. (Also see: Scleroderma Family and DNA Registry) |
| Single-nucleotide polymorphisms in the SPARC gene are not associated with susceptibility to scleroderma. Single-nucleotide polymorphisms (SNPs) in the SPARC gene are reportedly linked to scleroderma in four ethnic groups: Choctaw Indians, Caucasians, African Americans and Mexican Americans. Conclusions. SNPs in the SPARC gene are not associated with susceptibility to scleroderma. This research adds to the genetic knowledge of the SPARC gene by identifying five novel SNPs spanning the whole gene and inserting these within the context of clearly defined haplotypes. PubMed. Rheumatology (Oxford). 2004 Nov 16. |
| Scleroderma Care and Research Journal (PDF) This journal for physicians focuses on elevating the standards of care for digital ischemia in scleroderma. Articles include The Genetics of Scleroderma: What Every Rheumatologist Should Know, as well as Digital Ulceration and Critical Digital Ischemia in Scleroderma. Journal of the Scleroderma Clinical Trials Consortium (SCTC) Vol 1, No. 2, Winter 2003. (Also see: Scleroderma DNA and Family Registry, and Digital Ulcers) |
| Genomic instability in scleroderma. Evidence of acquired genetic damage in this disorder may be important in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer. PubMed. Asian Pac J Allergy Immunol. 2004 Jun-Sep;22(2-3):153-8. (Also see: Scleroderma and Cancer) |
| Choctaw Study |
| Genetic signatures of pre-expansion bottleneck in the Choctaw population of Oklahoma. This investigation utilizes genome-scan data on 175 dinucleotide loci from 76 Choctaw individuals to seek genetic evidence of the demographic history of the Choctaw Nation. PubMed. Am J Phys Anthropol. 2004 Aug;124(4):373-9. |
| Candidate Gene Regions Associated with Systemic Sclerosis (SSc): A Family-Based Association Study Using TDT Analysis. These data from a general SSc population confirm genetic associations previously reported in the Choctaw. The association of SSc with chromosomal region 1q42 suggests that a gene (or genes) in this area confer(s) a more generalized susceptibility to autoimmunity because this region has also been linked to SLE, RA, and type I diabetes. Maureen D. Mayes. ACR Conference Oct. 2003. |
| NIH-Funded Native American Study Finds Gene Site Associated With Scleroderma. A study blending modern-day genetic marker research and century-old tribal records has identified a chromosomal site associated with the connective tissue disease scleroderma in Oklahoma Choctaw Native Americans. Although scleroderma affects members of all ethnic groups, the disorder is particularly prevalent among the Choctaw. National Institutes of Health 10-29-1998. |
| DNA |
| New Research Shows One in 200 People Born with DNA Mutation That Can Lead to Devastating, Often Fatal Disease. Landmark research finding that one in every 200 people has a DNA mutation that could potentially cause a mitochondrial disease in them or their offspring. Market Watch. 08/11/08. |
| Genes Add Up Risk Of Autoimmune Disease. Geneticists have identified a link between the number of copies of a specific gene an individual has and their susceptibility to autoimmune diseases like lupus that affect the whole body. Research using DNA has revealed that people who have a below average number of copies of a gene, known as FCGR3B, have an increased risk of developing diseases caused when the body's immune system attacks its own tissue. Medical News Today. 05/25/07. (Also see: Lupus and Autoimmunity) |
| Scientists to unlock genes behind common serious illnesses. The biggest DNA analysis of whole human genomes will shed light on why some people are more at risk of developing a serious illness. They are examining 15,000 markers for genetic variations relating to another four diseases - breast cancer, autoimmune thyroid disease, multiple sclerosis, and ankylosing spondylitis. Guardian Unlimited. 04/14/07. (Also see: Thyroid Disease, Diabetes, and Multiple Sclerosis) |
| NALP1 in Vitiligo-Associated Multiple Autoimmune Disease. DNA sequence variants in the NALP1 region are associated with the risk of several epidemiologically associated autoimmune and autoinflammatory diseases, implicating the innate immune system in the pathogenesis of these disorders. New England Journal of Medicine. Vol 356:1216-1225 March 22, 2007 Number 12. |
| Unstabilized DNA breaks in lymphocytes of patients with systemic sclerosis. Our results indicate that in SSc patients there is an interference in the protective cellular mechanisms, normally stabilizing DNA breaks. PubMed. Eur J Dermatol. 2006 May-Jun;16(3):258-61. (Also see: What are Antibodies?) |
| HLA Markers for Susceptibility and Expression in Scleroderma. HLA alleles play a role in susceptibility to scleroderma and its disease expression. J Rheumatol. 2005 August;32:1481-7. |
| HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms. The HLA complex harbour both disease predisposing genes which are quite specific for some autoimmune diseases (e.g. HLA-B27 for ankylosing spondylitis) and others which may be more common for several diseases. PubMed. Transpl Immunol. 2005 Aug;14(3-4):175-82. |
| Skewed X chromosome inactivation in blood cells of women with scleroderma. Skewed XCI mosaicism may play a significant role in the pathogenesis of SSc. PubMed. Arthritis Rheum. 2005 May;52(5):1564-1570. |
| Shared gene expression profiles in individuals with autoimmune disease and unaffected first-degree relatives of individuals with autoimmune disease. Results support the hypothesis that these variations in gene transcript levels are associated with family resemblance rather than clinical manifestations of disease. PubMed. Hum Mol Genet. 2005 Apr 6. |
| Identification of novel targets in scleroderma: update on population studies, cDNA arrays, SNP analysis, and mutations. The identification of potential candidates for gene therapy or disease-specific targets amenable to pharmacologic intervention will benefit patients with systemic sclerosis who are currently being treated for their symptoms and not the disease process itself. PubMed. Curr Opin Rheumatol. 2003 Nov;15(6):766-71. |
| Systemic and cell type-specific gene expression patterns in scleroderma skin. The results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease. PubMed. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12319-24. |
| Ethnicity, Race, and Geographical Regions |
| Ethnicity Influence On Clinical And Immunological Manifestations In Systemic Sclerosis: Analysis Of 1139 Brazilian Patients. Ethnicity was associated with differences in the clinical and immunological presentation in a large national SSc cohort in Brazil. P. D. Sampaio-Barros AB0528 EULAR 2007. |
| Ethnic Disparities Among Patients with Pulmonary Hypertension Associated with Systemic Sclerosis. In this cohort of patients, African Americans were more likely to have dcSSc. Among patients with PH, African Americans presented at a younger age than their Caucasian counterparts. Incidence of diastolic dysfunction was higher in the PH population. J Rheumatol 2007 June;34:1277-82. (Also see: Pulmonary Hypertension) |
| Prevalence of renal involvement in Indian patients with systemic sclerosis. SRC (scleroderma renal crisis) is very rare in Indian patients with SSc. However, non-renal crisis abnormalities appear to be as common in Indian patients as compared to the western literature. PubMed. Indian J Med Sci. 2007 Feb;61(2):91-6. (Also see: Renal Involvement) |
| Pulmonary involvement in systemic sclerosis (SSc): Associations with genetic, serologic, sociodemographic, and behavioral factors. Early pulmonary involvement in SSc appears to be influenced by several factors delineated by ethnicity, including racial, socioeconomic, behavioral, and serologic determinants. PubMed. Arthritis Rheum. 2007 Feb 28;57(2):318-326. (Also see: Pulmonary Involvement) |
| Disease Subsets, Antinuclear Antibody Profile, and Clinical Features in 127 French and 247 US Adult Patients with Systemic Sclerosis. There are disease classification and SSc-related serum autoantibody differences between French and American patients with SSc. These differences help to explain variations in clinical features reported from different geographic regions. J Rheumatol 2007 January;34:104–9. (Also see: Antibodies) |
| Clinical Features in Arab and Jewish Patients with Systemic Sclerosis in North Israel. This data could support potential influences of ethnic origin on the pathogenesis of SSc and indicates further extension to large group and genetic studies. A. Balbir-Gurman. FRI0319 EULAR 2006. |
| Racial Variation in Clinical and Immunological Manifestations of Systemic Sclerosis. After adjusting for gender, disease classification, and disease duration, whites and blacks with SSc differ in some clinical and immunological manifestations of disease. Whether these differences can be attributed to genetic or environmental factors remains unknown. J Rheumatol 2006 February;33:263-8. |
| Race, Scleroderma, and Survival: Why Is There a Difference? Multiple studies have noted that race/ethnicity influences disease expression and outcome in systemic sclerosis. For example, compared to white Americans, African Americans have earlier disease onset, more frequently have diffuse cutaneous involvement, have increased severity of lung disease, and less frequently have anticentromere antibody positivity, which is a marker of more mild disease. Looking specifically at mortality, Laing, et al found that black women with scleroderma had a worse age-adjusted survival rate than did white women with scleroderma. J Rheumatol. 2005 October;32:1873. Editorial. |
| Epidemiology of systemic sclerosis in northwest Greece 1981 to 2002. The incidence and prevalence of SSc in northwest Greece were found to be lower than those of the USA and Australia, and higher than those of northern European countries and Japan. PubMed. Semin Arthritis Rheum. 2005 Apr;34(5):714-20. |
| Scleroderma in Australian aborigines. Scleroderma (systemic sclerosis) has not been reported before in Australian Aborigines. However, scleroderma does occur in indigenous Australians but further studies are needed to confirm the apparent infrequency of centromere-associated limited scleroderma (which is the commonest form of scleroderma in our Caucasian population). PubMed. Intern Med J. 2005 Jan;35(1):60-2. |
| The Influence of Renal Disease and Race on In-Hospital Mortality Among Patients with Systemic Sclerosis. During hospitalizations for SSc patients, renal disease was associated with an almost two-fold risk of in-hospital mortality. Black patients and other non-white patients also appear to experience an elevated risk of death during their hospital stays. Paul J. Nietert. 1050/430. ACR 2004. (Also see: Renal Involvement) |
| Racial disparities noted in immune system genes. African Americans were significantly more likely to carry genetic variants known to stimulate the inflammatory response. At the same time, genotypes known to dampen the release of anti-inflammatory proteins were more common among African Americans. Other disorders associated with the inflammatory response include premature labor, transplant rejection and autoimmune disorders such as multiple sclerosis and scleroderma - again, all more common among African Americans. EurekAlert! 12/01/04. |
| Profile of Antinuclear Antibodies (ANA) in 153 French Patients with Systemic Sclerosis (SSc). Comparison with a Series of 247 US SSc Patients. ANA profile is very similar between SSc patients from French and US centres with a major difference for anti-RNP polymerase III antibodies. As anti-RNA polymerase III antibodies have been described in SSc patients with extensive cutaneous [3] and a high frequency of renal involvement, clinical and epidemiological studies are in progress to explore this difference. O. C. Meyer. FRI0317 EULAR 2004. (Also see: Antibodies) |
| Prevalence of systemic sclerosis in a French multi-ethnic county. The higher prevalence observed for non-Europeans could support potential influences of ethnic origin on the pathogenesis of SSc. PubMed. Rheumatology (Oxford). 2004 Jun 22. |
| Systemic Sclerosis (SSc) in the Northeastern Thais: Clinical Data in 506 Patients. In Thai patients, diffuse scleroderma (dSSc) was more common than Limited Scleroderma (lSSc) with higher prevalence of internal organ involvement. Cardiopulmonary complication is the main cause of death. S. Suwannaroj. FRI0307 EULAR 2004. |
| Ethnic Differences in Cytotoxic T Lymphocyte Associated Antigen 4 Genotype Associations with Systemic Sclerosis. Our data show that the exon 1 (+49) polymorphism of the CTLA-4 gene is associated with systemic sclerosis in African Americans. J Rheumatol No. 1 Jan. 2004;31:85-7. |
| Prevalence of Systemic Sclerosis (SSc) in a French Urban Multi Ethnic County. Despite overlapping confidence intervals, the higher prevalence observed for non-Europeans could support potential influences of ethnic origin on the pathogenesis of SSc. V. Le Guern. SAT0200 EULAR 2003. |
| Prevalence of skin diseases in Ibadan, Nigeria. Allergic conditions have increased; connective tissue disorders, such as systemic lupus erythematosus, scleroderma, and discoid lupus erythematosus, have also increased. PubMed. Int J Dermatol. 2004 Jan;43(1):31-6. |
| Racial Variation in Clinical, Serologic, and Immunologic Manifestations of Systemic Sclerosis (SSc). This is the largest cohort study of its kind involving AAs (African Americans) with SSc. Results indicate that AAs have more severe disease than their Caucasian counterparts. Disease occurs at a younger age in AA patients, and they are more likely to have significant impairment of their lung function, a major cause of mortality in SSc patients. Holly C. Mitchell. ACR Conference Oct. 2003. |
| Ethnicity and race and systemic sclerosis: how it affects susceptibility, severity, antibody genetics, and clinical manifestations. Most studies have suggested that ethnic factors impact significantly on systemic sclerosis. Although these facts do not entirely rule out socioeconomic factors associated with ethnicity, nevertheless ethnicity has an important impact on the pathogenesis of systemic sclerosis, perhaps because of genetic factors. PubMed. Curr Rheumatol Rep 2003 Apr;5(2):160-7. |
| Influence of Genetic Background and Serological Features in Italian Patients with Systemic Sclerosis. TNF RII-GG Genotype Associate with the Diffuse Subset. These data indicate that the single nucleotide polymorphism in exon 6 of the TNFRII gene seems to be associated with susceptibility to SSc and may contribute to the phenotypic manifestations of dcSSc. B. Tolusso. FRI0116 EULAR 2003. |
| Familial CRST Syndrome with Sicca Complex |
| Familial CRST syndrome with sicca complex. PubMed J Rheumatol. 1977 Spring;4(1):53-8. |
| Familial Progressive Systemic Sclerosis (FPSS) |
| Familial Progressive Scleroderma is a form of systemic scleroderma that is known to be hereditary. |
| Familial progressive systemic scleroderma. This isolate is a group of families who have been inbreeding since 1660 and now have the highest gene frequencies for sickle cell anemia and oculocutaneous albinism in the United States. Arch Dermatol 1975 Jan;111(1):81-5 Medline. |
| Familial scleroderma (FS): nature, nurture or both? Familial limited scleroderma has a longer prediagnostic latency than familial diffuse scleroderma. FS is likely under-ascertained. In limited scleroderma, Raynaud's or first symptom onset is possibly more genetically determined. A diagnosis due to second symptom onset is more environmentally determined. (PubMed) Intern Med J. 2008 Apr;38(4):235-42. (Also see: Difficult Diagnosis and Causes of Scleroderma: Environmental) |
| Familial progressive systemic sclerosis (scleroderma): immunological analysis of two patients and six siblings from a single kindred. Clin Exp Immunol 1982 Nov;50(2):275-82 Medline. |
| Dee: Daughter of Scleroderma Patient Three years ago my mother was diagnosed with scleroderma. My aunt died of scleroderma last year... |
| Iris: Family History of Scleroderma Is there anyone else who feels that their family has a history of scleroderma? |
| Rosemary F: Surviving Daughter of Diffuse Scleroderma Patient She tried to explain it, but it was hard for me to comprehend the disease's symptoms. Mom said that it was the same thing that her oldest sister died from... |
| Stephanie D: Scleroderma/Heparin-Induced Thrombocytopenia If I receive heparin again I will certainly die... |
| Genetics and Scleroderma |
| It's Not All in the Genes. Your genes are not your destiny. Lifestyle and diet can play an important role on your genes. You can change the outcome even if it is "written" otherwise in your genes. RedOrbit. 06/30/08. (Also see: Alternative Therapies) |
| Dartmouth researchers discover gene signatures for scleroderma. Distinct genetic profiles can discern different groups of patients with scleroderma. This discovery of distinguishing molecular subtypes within the disease offers new insight into the complexity of a poorly understood and hard to treat illness and opens a window for better diagnosis and targeted therapies. Genetic Engineering & Biotechnology News. July 15, 2008. (Also see: Types of Scleroderma) |
| Familial Clustering of Auto-immune Diseases in Patients with Systemic Sclerosis. The high prevalence of other auto-immune diseases in families of SSc patients strongly suggests that there may be one shared gene or group of genes that predisposes to multiple autoimmune diseases. Marie Hudson. 1202/434. ACR 2007. |
| Genetic basis for systemic sclerosis. Investigations into the genetics of systemic sclerosis may shed light on the complex pathophysiology of this disease, help to identify factors that predict organ involvement, and suggest new treatment strategies. Science Direct. Oct 2007. (Also see: Causes of Scleroderma: Silica, Solvents, and Environmental Factors) |
| There's no cure, but scleroderma can be managed. We don't know what causes scleroderma. Researchers suspect that there is a genetic link. The theory is that while a specific genetic trait predisposes the individual, scleroderma will only occur after exposure to some environmental agent, such as a particular virus. Post-Bulletin. Mayo Clinic. 06/04/07. (Also see: Causes of Scleroderma: Infections, and What is Scleroderma?) |
| Genetic Association Studies in Systemic Sclerosis: More Evidence of a Complex Disease. Systemic sclerosis (SSc) clearly falls into the category of complex genetic disease, with well recognized variability in clinical and serological presentation and intricate underlying mechanisms, which involve vascular and immune activation within a fibrotic process. J Rheumatol 2007 May;34:903 Editorial. (Also see: Causes of Scleroderma: Environment) |
| Association of Polymorphisms in the IL1B and IL2 Genes with Susceptibility and Severity of Systemic Sclerosis. IL1B and IL2 gene polymorphisms may be involved in susceptibility to SSc. Moreover, the IL2-384-G allele may be a marker for the limited phenotype of SSc. J Rheumatol 2007 May;34:997-1004. (Also see: Limited Scleroderma) |
| Update on pathophysiology of scleroderma with special reference to immunoinflammatory events. Scleroderma or systemic sclerosis (SSc) is a complex disease in which the vasculopathy and the activation of the immune system with production of inflammatory mediators lead to dysregulated fibroblast activation. The resulting excessive deposition of collagens and other extracellular matrix proteins ends in fibrosis and organ dysfunction. The cause is unknown, but environmental factors are thought to play a role by triggering abnormal responses in genetically susceptible hosts. PubMed. Ann Med. 2007;39(1):42-53. (Also see: What is Scleroderma) |
| Distinct Genetic Signatures In Systemic Sclerosis Subtypes: Insights From Gene Expression Profiling. Subtle variation in some of these genes which regulate critical pathological pathways in SSc could determine the disease subtype and hence could be potential targets for candidate gene association studies. Sudeep P. Pushpakom. 1835/507 ACR 2006. |
| Disease Features, Disease Type, HLA Types, and Autoantibody Profile in 17 Multicase SSc Families. These findings suggest that the concordance for disease type and SSc specific autoantibodies is more common among SSc family members and the ACA positive limited SSc has a stronger genetic basis, and that the familial SSc does not represent a unique disease subset. Shervin Assassi. 1153/412 ACR 2006. (Also see: Scleroderma Family Registry and DNA Repository) |
| The X chromosome and systemic sclerosis. These observations, reproduced in other female-predominant autoimmune diseases, strongly support the role of the X chromosome in conferring susceptibility to tolerance breakdown and open novel scenarios to emphasize the unknown etiopathogenesis of systemic sclerosis. PubMed. Curr Opin Rheumatol. 2006 Nov;18(6):601-605. (Also see: Causes of Scleroderma: Hormones & Chromosomes) |
| IL13RA2 Gene Polymorphisms Are Associated with Systemic Sclerosis. Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease. J Rheumatol 2006 October;33:2015-9. |
| In-depth Analysis Of Human Genetic Variation Will Enable Scientists To Identify Genetic Risk Factors For Common Immune Diseases. The work lays the scientific foundation for future efforts aimed at uncovering the genetic roots of immune-related diseases. Medical News Today. 09/28/06. |
| Antinuclear Antibodies and Non-SSc Autoimmune Diseases in First-Degree Relatives of Scleroderma Patients: Data from the Scleroderma Family Registry and DNA Repository. This is the largest scleroderma family study to date. The results demonstrate no significant difference between the frequencies of ANA positivity in first-degree relatives compared to controls. In our population, a positive ANA was frequently associated with a diagnosed autoimmune disease. Jo Elle G. Peterson. 1556/332. ACR 2005. (Also see: Antibodies) |
| Monozygotic twins clinically discordant for scleroderma show concordance for fibroblast gene expression profiles. A stronger genetic predisposition to SSc (than can be detected clinically) is apparent at the molecular level in skin fibroblasts. PubMed. Arthritis Rheum. 2005 Oct;52(10):3305-14. |
| Genetics of scleroderma: update on single nucleotide polymorphism analysis and microarrays. Recent family, twin, and genetic association studies suggest a genetic basis for the susceptibility to systemic sclerosis or scleroderma. Candidate genes or pathways identified through microarrays can be explored as potential biomarkers, used for molecular phenotyping of systemic sclerosis, or targeted for future genetic association studies. PubMed. Curr Opin Rheumatol. 2005 Nov;17(6):761-7. |
| X Chromosome Monosomy: A Common Mechanism for Autoimmune Diseases. Chromosome instability is common to women with SSc and AITD (autoimmune thyroid disease) and haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases. PubMed. J Immunol. 2005 Jul 1;175(1):575-578. (Also see: Thyroid Disease) |
| Genetic factors predisposing to fibrosis in systemic sclerosis. Identification of genetic factors involved in the susceptibility to fibrosis of systemic sclerosis would lead to a better understanding of physiopathological mechanisms of this disease and to therapeutic targets using immunomodulation with drugs, such as already performed in rheumatoid arthritis. PubMed. Rev Med Interne. 2005 Apr;26(4):294-303. (Also see: Skin Fibrosis) |
| Transgenic analysis of scleroderma: understanding key pathogenic events in vivo. These experiments implicate the IL-4 ligand-receptor axis in the development of skin fibrosis. Modern molecular genetic methods have allowed better understanding of established mouse models of scleroderma and also facilitated the development of new and better defined mouse strains for investigating the pathogenesis of the disease. PubMed. Autoimmun Rev. 2004 Jun;3(4):285-93. |
| Keys to unlocking the mysteries of rheumatic autoimmune disease. Identification of susceptibility genes and dysregulated biological pathways for these diseases is likely to foster development of novel diagnostic and therapeutic approaches that are increasingly tailored to the underlying pathological mechanisms. PubMed. Minn Med. 2004 May;87(5):46-51. |
| Association of killer cell immunoglobulin-like receptors with scleroderma. A genetic contribution has been demonstrated, and genes influencing activation of the immune system have been potentially identified as candidate genes in this process. The repertoire of killer cell immunoglobulin-like receptors (KIRs) that are involved in the activation of T cells and natural killer cells is highly variable. The genetic combination of KIR2DS2+ and KIR2DL2- is associated with scleroderma. PubMed. Arthritis Rheum. 2004 May;50(5):1561-5. |
| Gene expression signatures for autoimmune disease in peripheral blood mononuclear cells. The relatively new technology of DNA microarrays offers the possibility to probe the human genome for clues to the pathogenesis and treatment of human disease. Of special interest are studies that have used peripheral blood samples because, unlike tissue biopsies, these are readily available from all subjects. Using this approach, patterns of gene expression can be detected that distinguish patients with autoimmune conditions from normal subjects. PubMed. Arthritis Res Ther. 2004;6(3):120-8. |
| Profiles of gene expression in human autoimmune disease. All autoimmune individuals, including unaffected first-degree relatives, share a common gene expression profile that is completely distinct from the immune profile. These data argue that that there is a constant pattern of gene expression in autoimmunity that is independent of the specific autoimmune disease and clinical parameters associated with any individual autoimmune disease. PubMed. Cell Biochem Biophys. 2004;40(2):81-96. |
| Vascular Injury in Systemic Sclerosis: Angiotensin-converting Enzyme Insertion/Deletion Polymorphism. ACE D allele frequency of the I/D polymorphism was associated with an increased risk of SSc, suggesting a genetic contribution to the disease. PubMed. Curr Rheumatol Rep. 2004 Apr;6(2):149-55. |
| Coexistence of HLA-B*08 and HLA-B*18 in Four Siblings with Lichen sclerosus. HLA-B*08 and HLA-B*18 alleles were detected in children with LS, but not in a healthy sister. None of the patients had autoimmune disease. In our opinion, coexistence of these two alleles may play a role in the development of LS. PubMed. Dermatology. 2004; 208(1): 64-6. (Also see: Lichen Sclerosis) |
| Genetic Instability in Scleroderma. We have observed further evidence of acquired genetic damage in scleroderma and such genetic instability may be of importance in explaining both the aetio-pathogenesis and the association with common cancer. P. J. Roberts-Thomson. OP0125 EULAR 2003. |
| Gene profiling to start with Morphea In the last quarter we have identified genes in all of the major skin cell types that can be used as reference points for gene expression. We have also identified genes that are highly activated in each cell type in response to inflammation. This will allow us to determine which cell types are becoming activated. Scleroderma Assoc. of NSW. August 2003 (Also see: Morphea) |
| Gene Expression in Scleroderma. This study will be the most thorough study of gene expression in Scleroderma conducted to date. By correlating gene expression data with clinical history and treatment record it may be possible to determine the role of individual cell types in disease progression and to determine the role of inflammation at different stages of the disease. This information should significantly improve treatment. Scleroderma Assoc. of NSW. May 2003. |
| Common Fabric of Human Autoimmune Disease Revealed by Gene Expression Profiling. We find that all individuals with one of four major autoimmune diseases share a common gene expression signature. We can identify autoimmune individuals with 100% accuracy using mathematical scores based upon levels of expression of gene transcripts. T. Aune. SP0057 EULAR 2003. |
| Systemic Sclerosis, State of the Art. The aetiopathogenesis of scleroderma is complex, but modern genetic approaches have provided the tools with which to address the most vexing aspects of the pathology, namely the overproduction of extracellular matrix by connective tissue fibroblast. C. Black. SP0174 EULAR 2003. (Also see: ISN: Prof. Carol Black) |
| Systemic sclerosis: the susceptible host (genetics and environment). Multi-center collaborative efforts with research paradigms that integrate genetic and environmental factors (including sociodemographic variables) will be required to elucidate the contribution of environment and genetics in the pathogenesis of SSc. PubMed. Rheum Dis Clin North Am. 2003 May;29(2):211-37. |
| Human Genome Project and Scleroderma |
| Genetic Alliance Resources. Genetic Alliance is a network of thousands of health related organizations, including more than 600 advocacy organizations. Genetic Alliance. |
| Scleroderma Gene Project Advances to Human Tissue Study. The power of the Human Genome Project has been harnessed for scleroderma research at the Centre for Immunology, St Vincent's Hospital. Scleroderma Association of New South Wales, Inc. |
| Human Genome Project Boosts Scleroderma Research. A group at the Centre for Immunology, St Vincent's Hospital Sydney is at the vanguard of this research, employing the latest "Gene array" technology to determine the patterns of gene expression that occur in scleroderma. Scleroderma Association of New South Wales, Inc. |
| Scleroderma Registries |
| Scleroderma Family Registries are available in many countries and they are very important for tracking the incidence of scleroderma as well as providing valuable clues for research. If you or a family member has scleroderma, consider registering today! ISN. |
| Shared Autoimmunity |
| Co-occurrence of celiac disease and other autoimmune diseases in celiacs and their first-degree relatives. These results indicate that the presence of insulin dependent diabetes mellitus within our celiac disease families may be due to shared genetic susceptibility predisposing to these diseases or autoimmune diseases in general. (UnBound Medline) S.L. Neuhausen. J Autoimmun 2008 Aug 7. (Also see: Celiac Disease and Shared Autoimmunity) |
| Overlap syndromes in the context of shared autoimmunity. "Shared autoimmunity" is the term being used for the presence of autoimmune rheumatic diseases in several members of the same family, the concurrence of autoimmune rheumatic with non-rheumatic diseases in relatives of patients, the presence of autoantibodies in sera from healthy relatives of autoimmune-disease patients, the development of two or more autoimmune rheumatic diseases in one patient and the interplay of genetic and environmental factors leading to the presence of several autoimmune disease and/or their autoantibodies in families. PubMed. Autoimmunity. 2005 May;38(3):219-23. (Also see: Overlap Syndrome: MCTD) |
| Twins and Siblings With and Without Autoimmune Diseases |
| Open Enrollment (A 5-year study) |
 Families with Twins or Siblings where one has Systemic Rheumatic Disorders (Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis, Lupus, Scleroderma, or Myositis) and one does not. The goal of study 03-E-0099 is to assess why one twin or sibling developed disease and why the other brother or sister did not.
The siblings may or may not be twins, but must be of the same gender and be within a 3-year age difference. Biological parents, or, in some cases, children, will also be included in the study.
Families may enroll at the NIH Clinical Center in Bethesda, Maryland, just 9 miles north of Washington, DC or at their local physician’s office. Transportation assistance may be available and there is no charge for study-related evaluations and medical tests.
For information on the study, call the NIH patient recruiting office toll free at 1-800-411-1222 (For TTY: 1-866-411-1010). National Institutes of Health Clinical Center (NIH). 11/25/05. (Also see: Scleroderma Research Registries) |
| Analysis of systemic sclerosis in twins reveals low concordance for disease and high concordance for the presence of antinuclear antibodies. PubMed Arthritis Rheum. 2003 Jul;48(7):1956-63. |
