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Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels
BACKGROUND: Fibromyalgia syndrome (FMS), a common, chronic, widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, has both genetic and environmental contributions. Patients and their parents have high plasma levels of the chemokine...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794536/ https://www.ncbi.nlm.nih.gov/pubmed/20041150 http://dx.doi.org/10.1371/journal.pone.0008480 |
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author | Feng, Jinong Zhang, Zhifang Li, Wenyan Shen, Xiaoming Song, Wenjia Yang, Chunmei Chang, Frances Longmate, Jeffrey Marek, Claudia St. Amand, R. Paul Krontiris, Theodore G. Shively, John E. Sommer, Steve S. |
author_facet | Feng, Jinong Zhang, Zhifang Li, Wenyan Shen, Xiaoming Song, Wenjia Yang, Chunmei Chang, Frances Longmate, Jeffrey Marek, Claudia St. Amand, R. Paul Krontiris, Theodore G. Shively, John E. Sommer, Steve S. |
author_sort | Feng, Jinong |
collection | PubMed |
description | BACKGROUND: Fibromyalgia syndrome (FMS), a common, chronic, widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, has both genetic and environmental contributions. Patients and their parents have high plasma levels of the chemokines MCP-1 and eotaxin, providing evidence for both a genetic and an immunological/inflammatory origin for the syndrome (Zhang et al., 2008, Exp. Biol. Med. 233: 1171–1180). METHODS AND FINDINGS: In a search for a candidate gene affecting inflammatory pathways, among five screened in our patient samples (100 probands with FMS and their parents), we found 10 rare and one common alleles for MEFV, a gene in which various compound heterozygous mutations lead to Familial Mediterranean Fever (FMF). A total of 2.63 megabases of genomic sequence of the MEFV gene were scanned by direct sequencing. The collection of rare missense mutations (all heterozygotes and tested in the aggregate) had a significant elevated frequency of transmission to affecteds (p = 0.0085, one-sided, exact binomial test). Our data provide evidence that rare missense variants of the MEFV gene are, collectively, associated with risk of FMS and are present in a subset of 15% of FMS patients. This subset had, on average, high levels of plasma IL-1β (p = 0.019) compared to FMS patients without rare variants, unaffected family members with or without rare variants, and unrelated controls of unknown genotype. IL-1β is a cytokine associated with the function of the MEFV gene and thought to be responsible for its symptoms of fever and muscle aches. CONCLUSIONS: Since misregulation of IL-1β expression has been predicted for patients with mutations in the MEFV gene, we conclude that patients heterozygous for rare missense variants of this gene may be predisposed to FMS, possibly triggered by environmental factors. |
format | Text |
id | pubmed-2794536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27945362009-12-30 Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels Feng, Jinong Zhang, Zhifang Li, Wenyan Shen, Xiaoming Song, Wenjia Yang, Chunmei Chang, Frances Longmate, Jeffrey Marek, Claudia St. Amand, R. Paul Krontiris, Theodore G. Shively, John E. Sommer, Steve S. PLoS One Research Article BACKGROUND: Fibromyalgia syndrome (FMS), a common, chronic, widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, has both genetic and environmental contributions. Patients and their parents have high plasma levels of the chemokines MCP-1 and eotaxin, providing evidence for both a genetic and an immunological/inflammatory origin for the syndrome (Zhang et al., 2008, Exp. Biol. Med. 233: 1171–1180). METHODS AND FINDINGS: In a search for a candidate gene affecting inflammatory pathways, among five screened in our patient samples (100 probands with FMS and their parents), we found 10 rare and one common alleles for MEFV, a gene in which various compound heterozygous mutations lead to Familial Mediterranean Fever (FMF). A total of 2.63 megabases of genomic sequence of the MEFV gene were scanned by direct sequencing. The collection of rare missense mutations (all heterozygotes and tested in the aggregate) had a significant elevated frequency of transmission to affecteds (p = 0.0085, one-sided, exact binomial test). Our data provide evidence that rare missense variants of the MEFV gene are, collectively, associated with risk of FMS and are present in a subset of 15% of FMS patients. This subset had, on average, high levels of plasma IL-1β (p = 0.019) compared to FMS patients without rare variants, unaffected family members with or without rare variants, and unrelated controls of unknown genotype. IL-1β is a cytokine associated with the function of the MEFV gene and thought to be responsible for its symptoms of fever and muscle aches. CONCLUSIONS: Since misregulation of IL-1β expression has been predicted for patients with mutations in the MEFV gene, we conclude that patients heterozygous for rare missense variants of this gene may be predisposed to FMS, possibly triggered by environmental factors. Public Library of Science 2009-12-30 /pmc/articles/PMC2794536/ /pubmed/20041150 http://dx.doi.org/10.1371/journal.pone.0008480 Text en Feng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Feng, Jinong Zhang, Zhifang Li, Wenyan Shen, Xiaoming Song, Wenjia Yang, Chunmei Chang, Frances Longmate, Jeffrey Marek, Claudia St. Amand, R. Paul Krontiris, Theodore G. Shively, John E. Sommer, Steve S. Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels |
title | Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels |
title_full | Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels |
title_fullStr | Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels |
title_full_unstemmed | Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels |
title_short | Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels |
title_sort | missense mutations in the mefv gene are associated with fibromyalgia syndrome and correlate with elevated il-1β plasma levels |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794536/ https://www.ncbi.nlm.nih.gov/pubmed/20041150 http://dx.doi.org/10.1371/journal.pone.0008480 |
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