Ethnicity, Race, Geography
Familial CRST w/ Sicca
Genetics and Scleroderma
|Homocysteine/MTHFR C677T Gene Mutation
Human Genome Project
Twins and Siblings Study
Researchers have found some genes associated with the development of systemic sclerosis (scleroderma).
There are several types of scleroderma that are known to run in families, such as Familial CRST w/ Sicca, and Familial Progressive Systemic Sclerosis. Genes that predispose to scleroderma were found by studying the Choctaw Indian Tribe of Oklahoma, where those with scleroderma all shared a common ancestor.
This does not mean, however, that scleroderma is a "genetic illness" per se. They estimate that it is genetic in only 2% of scleroderma patients. However, there are some genes that set the stage for the development of autoimmune disease in general, and scleroderma in particular.
Should a parent with scleroderma worry about their child acquiring scleroderma? No, not unless there is a known pattern of scleroderma already established in the family.
However, that said, there is about a 30% chance that children from parents with any autoimmune disease might eventually develop any autoimmune disease or autoantibodies, or, more commonly, just a symptom or two of any autoimmune disease — due to general inherited and/or lifestyle susceptibility. (Also see What is Scleroderma?, Autoimmune Diseases, and Pregnancy and Scleroderma)
There’s a Gene Mutation That Makes You a Reckless Drunk, Study Suggests. New research suggests there may be a genetic explanation for why some people are more likely to get out of control under the influence of alcohol. Time Healthland, 11/19/2015.
Parental Influence on Systemic Sclerosis (SSc). Birth order and maternal/paternal age at conception do not significantly affect SSc development even though heritable risk of SSc is observed. PubMed, Arthritis Care Res (Hoboken), 2014 Apr 22.
Systemic sclerosis, birth order and parity. Parity, age at first pregnancy and the gender of the first child are not relevant factors in our understanding of the epidemiology and pathogenesis of SSc. PubMed, Int J Rheum Dis, 2013 Nov 29.
It was discovered that systemic scleroderma is sometimes hereditary through genetic research done on the Choctaw Indian Tribe of Oklahoma, where all of the scleroderma patients have one common ancestor. There is also an apparent scleroderma cluster (of unknown cause) in the Kahnawake Indian Tribe of Quebec, Canada.
Race and Ethnicity
Familial CRST syndrome with sicca complex. PubMed, J Rheumatol. 1977 Spring;4(1):53-8.
(Case Report) Familial Occurrence of Collagen Diseases: II. Progressive Systemic Sclerosis and Dermatomyositis. A case report of progressive systemic scleroderma (mother), lupus (daughter), and dermatomyositis (son) in the same family. Wiley, Journal of Internal Medicine, .
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…
A candidate gene study identifies a haplotype of CD2 as novel susceptibility factor for systemic sclerosis (SSc). Our study establishes CD2 as a new susceptibility factor for SSc, in a European Caucasian population, confirming the sharing of autoimmune risk factors by SSc and rheumatoid arthritis. PubMed, Clin Exp Rheumatol, 07/01/2016.
Negatively–charged (NTC) amino acids at the peptide–binding pocket of HLA–DPB1 alleles are associated with susceptibility to anti–opoisomerase I (ATA)–positive systemic sclerosis (SSc). ATA–positive SSc patients share NCTs at the peptide–binding groove of HLA–DPB1 molecules. PubMed, Hum Immunol, 05/18/2016.
Whole Exome Sequencing (WES) for Identification of Potential Causal Variants for Diffuse Cutaneous Systemic Sclerosis. This study demonstrates the value of WES for the identification of novel gene variants and pathways that may contribute to scleroderma risk and/or severity. PubMed, Arthritis Rheumatol, 04/25/2016.
More complete genetic map of scleroderma disease makes more effective medications possible. The study has determined possible genetic associations of the different subtypes of the disease, especially the more aggressive ones. Science Daily, 04/08/2016.
Genetic and epigenetic abnormalities in systemic sclerosis (SSc). Further investigations of the interplay between genetics and epigenetics will be beneficial to elucidate the complex molecular cross–talk and heterogeneity in the SSc pathogenesis. PubMed, J Dermatol, 2016 Jan;43(1):10-8.
Epigenetics and systemic sclerosis. The environment can trigger epigenetic regulation that in turn establishes a molecular framework linking environmental exposures to genetics, leading to the disease process, possibly in a genetically predisposed host. PubMed, Semin Immunopathol, 07/11/2015.
Patients with Systemic Sclerosis (SSc) Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms. Polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of autoantibodies. PubMed, J Rheumatol, 2014 Feb 1.
Systemic Sclerosis (SSc) in Canada's North American Native (NAN) Population: Assessment of Clinical and Serological Manifestations. NAN patients with SSc have a distinct clinical phenotype. Our study provides a strong rationale to pursue further research into genetic and environmental determinants of SSc. Journal of Rheumatology, 2013 May 15.
Indoleamine 2,3 dioxygenase (IDO) gene polymorphisms correlate with CD8+ Treg impairment in systemic sclerosis. Our unprecedented data show that a specific IDO gene SNP is associated with an autoimmune disease such as systemic sclerosis. PubMed, Hum Immunol, 2013 Feb;74(2):166-9.
Genetics of scleroderma: implications for personalized medicine? Significant advances have been made in understanding the genetic basis of systemic sclerosis (scleroderma) in recent years which might lead to individualized monitoring and treatment. BMC Medicine, 2013, 11:9.
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.
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 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.
Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Most of the genetic variants associated with a particular autoimmune endocrine disease are shared between other systemic and organ-specific autoimmune and inflammatory diseases, such as rheumatoid arthritis, coeliac disease, systemic lupus erythematosus and psoriasis. PubMed, Nature Reviews Endocrinology, November 2013.
Telomere is the segment of DNA at the ends of chromosomes.
2014 ACR/ARHP Annual Meeting: Telomeres and the Aging Immune System. Although the clinical significance of telomere shortening in the context of chronic inflammation or advanced age is still not fully understood, it is an area of active investigation that is uncovering an important link to the immune response and to inflammatory conditions. The Rheumatologist, 01/01/2015.
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). Last verified March 2015. (Also see Scleroderma Research Registries and Causes of Scleroderma: Genetics)
Reading Voices of Scleroderma Books: Diana Kramer.
Sharing Scleroderma Awareness Bracelets: Deb Martin, Brenda Miller, Vickie Risner.
Thanks to UNITED WAY donors of Central New Mexico and Snohomish County!
Patricia Ann Black: Marilyn Currier, Shelley Ensz, Richard Howitt, Gerald and Pat Ivanejko, Juno Beach Condo Association, Keith and Rosalyn Miller, and Elaine Wible.
Gayle Hedlin: Daniel and Joann Pepper and Nancy Smithberg.
Janet Paulmenn: Anonymous, Shelley Blaser, Susan Book, Dennis and Pat Clayton, Grace Cunha, Cindy Dorio, Shelley Ensz, Nancy Falkenhagen, Jo Frowde, Margaret Hollywood, Karen Khalaf and Family, Susan Kvarantan, Bradley Lawrence, Jillyan Little, Michele Maxson, John Moffett, Joan-Marie Permison, John Roberts, Margaret Roof, and Maryellen Ryan.
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