| 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. |
| Birth Order |
| Separate influences of birth order and gravidity/parity on the development of systemic sclerosis. Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility. Cockrill T. (PubMed) Arthritis Care Res (Hoboken). 2010 Mar;62(3):418-24. |
| 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. |
| DNA |
| It's Not All in the Genes. Thus, when it comes to illness, health, behaviours, and life patterns, genes can predispose but they cannot predetermine. Because no two people are subjected to exactly the same input from the environment, not even the brains of genetically identical twins will have the same set of connections, nerve branches, and active chemical pathways. The Mark. 10/02/09. (Also see: Causes of Scleroderma) |
| 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. |
| Ethnicity, Race, and Geographical Regions |
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| 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. |
| Autoimmune diseases and autoantibodies in the first degree relatives of patients with systemic sclerosis (SSc). Our study implies varying degrees of risk for familial autoimmunity among subtypes of SSc and provides further support for common genetic and potentially environmental factors leading to SSc and lupus. Arora-Singh RK. (PubMed) J Autoimmun. 2010 Aug;35(1):52-7. |
| 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 |
| Updating the genetics of systemic sclerosis (SSc). The use of powerful molecular tools has shed light on the nature of the susceptibility genes for SSc and the pathophysiology of this disease. Postgenomic studies are now required to clarify the role of these genes. Y Allanore. (PubMed) Curr Opin Rheumatol. 2010 Jul 7. |
| UT scientists and clinicians are innovators in autoimmune and autoinflammatory disease research and care. Cutting-edge research at the UT Health Science Center at Houston includes the discovery of 10 to 15 genes that predispose people toward scleroderma, lupus and rheumatoid arthritis and the unearthing of four genes tied to ankylosing spondylitis. Rob Cahill. HealthCanal.com. 12/26/09. |
| New Genetic Link to Scleroderma Discovered. Scientists report they found a new region of the human genome associated with increased systemic scleroderma susceptibility. “With our latest discovery, we are probably a quarter of the way to finding the genes and pathways responsible forsystemic scleroderma.” Said Maureen D. Mayes, MD. ScienceDaily. 04/29/10. |
| Geneticists Hunt For Scleroderma Triggers. A study reported in the October 2009 Journal of Investigative Dermatology reports a closer connection between a gene profile for the profibrotic pathway TGF-beta and a tendency in some scleroderma sufferers to develop lung problems. Science Daily. 10/30/09. |
| BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians. Our results suggest that BANK1 gene confers susceptibility to systemic scleroderma (SSc) in general, and specifically to the diffuse SSc and anti-topoisomerase-I antibody subsets. B Rueda. Ann Rheum Dis. 8 October 2009. |
| Association of TNFSF4 (OX40L) polymorphisms with susceptibility to Systemic Sclerosis. It is increasingly being appreciated that multiple autoimmune diseases share common susceptibility genes. Polymorphisms in the TNFSF4 gene region are associated with susceptibility to SSc and its clinical and autoantibody subsets. TNFSF4 may be another gene that confers risk to multiple autoimmune diseases. Pravitt Gourh Ann Rheum Dis. 23 September 2009. (Also see: Polyautoimmunity) |
| 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) |
| 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) |
| Homocysteine and MTHFR C677T Gene Mutation |
| Plasma Homocysteine Levels and the Prevalence of Methylenetetrahydrofolate Reductase Gene C677T Polymorphism in Systemic Sclerosis. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc. Elevated Hcy levels may be associated with disease duration and the evolution of macrovascular disorders and pulmonary hypertension in SSc. Clinical Reviews in Allergy and Immunology, Volume 36, Numbers 2-3/June, 2009. |
| 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 |
| 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) |
| Heritability of vasculopathy, autoimmune disease, and fibrosis in systemic sclerosis (SSc): A population-based study. These data suggest that SSc pedigrees include more Raynaud's phenomenon, autoimmune inflammatory disease, and interstitial lung disease than would be expected by chance. In SSc pedigrees, genetic predisposition to vasculopathy is the most frequent risk among first-degree relatives. T. Frech. Arthritis Rheum. 2010 Mar 26;62(7):2109-2116. |
| Autoimmune diseases and autoantibodies in the first degree relatives of patients with systemic sclerosis (SSc). Our study implies varying degrees of risk for familial autoimmunity among subtypes of SSc and provides further support for common genetic and potentially environmental factors leading to SSc. Arora-Singh RK. (PubMed) J Autoimmun. 2010 Mar 9. |
| 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) |
| 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. |
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