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- Title
Discovery of Potential New Gene Variants and Inflammatory Cytokine Associations with Fibromyalgia Syndrome by Whole Exome Sequencing.
- Authors
Feng, Jinong; Zhang, Zhifang; Wu, Xiwei; Mao, Allen; Chang, Frances; Deng, Xutao; Gao, Harry; Ouyang, Ching; Dery, Kenneth J.; Le, Keith; Longmate, Jeffrey; Marek, Claudia; St. Amand, R. Paul; Krontiris, Theodore G.; Shively, John E.
- Abstract
Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder, we performed complete exome sequencing on a subset of FMS patients. Out of 150 nuclear families (trios) DNA from 19 probands was subjected to complete exome sequencing. Since >80,000 SNPs were found per proband, the data were further filtered, including analysis of those with stop codons, a rare frequency (<2.5%) in the 1000 Genomes database, and presence in at least 2/19 probands sequenced. Two nonsense mutations, W32X in C11orf40 and Q100X in ZNF77 among 150 FMS trios had a significantly elevated frequency of transmission to affected probands (p = 0.026 and p = 0.032, respectively) and were present in a subset of 13% and 11% of FMS patients, respectively. Among 9 patients bearing more than one of the variants we have described, 4 had onset of symptoms between the ages of 10 and 18. The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort.
- Subjects
CYTOKINES; FIBROMYALGIA; INFLAMMATION; MUSCULOSKELETAL system diseases; HUMAN genetic variation; COMPUTATIONAL biology; GENETIC polymorphisms; IMMUNE response
- Publication
PLoS ONE, 2013, Vol 8, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0065033