Personal+Genomics+Fibromyalgia

Cynthia Nicolosi crn2004@wildcats.unh.edu Personal Genomics Research Project: Fibromyalgia

**Abstract**
Fibromyalgia is a condition of chronic musculoskeletal pain that afflicts about 2% of the population. It is most common in women. The etiology of fibromyalgia is unknown, but recent studies have shown that a predisposition to the condition may be the result of specific gene polymorphisms. Of these, genes coding for the TRPV ion channels are of interest. This Wikispace gathers together current research on fibromyalgia, its treatment, and the connection between the TRPV genes and the TRPV channels which are implicit in the symptoms of pain associated with the disorder.

Background Summary

 * Fibromyalgia is a syndrome indicated by chronic musculoskeletal pain.
 * It effects about 2% to 4% of the population.
 * It is more common in women.
 * The etiology of Fibromyalgia is as yet unknown.
 * No evidence suggests that it is an autoimmune disease, or that it is owed to inflammation.
 * Some evidence indicates that it is neurological in origin insofar as it involves nociceptive pathways.
 * The implication of nociceptive pathways leads back to the genes which code for these pathways.
 * No actual diagnostic test exists for Fibromyalgia. Diagnosis is based solely on a patient’s subjective report of degrees and kinds of pain experienced.
 * As yet, there is no cure for Fibromyalgia, though pain can be managed with lifestyle and drug therapy.
 * Evidence suggests that a reduction in stress can ameliorate symptoms; hence, counseling or stress relieving activities (i.e., exercise) are often advised.
 * Some people find relief in alternative forms of medicine, such as massage therapy and acupuncture.


 * Introduction**

Fibromyalgia designates a condition of chronic musculoskeletal pain that can also include cognitive dysfunction, sleep disorders, and mood swings. It effects about 2% of the population and is most common in middle-aged women (NFA; ACR). Although there is no certain cause for fibromyalgia, two areas that have been implicated in its etiology are central nervous system nociceptive processing and psychological factors such as stress (Ablin et al., 2016; Lan & Chun-Hung, 2016; Sluka, 2016).

In recent times, studies have uncovered evidence that DNA may hold the key to understanding the etiology of fibromyalgia. Many researchers today are looking for genetic markers of fibromyalgia that might indicate if not a cause than at least a predisposition for the disease. Specific genes have been associated with the pain and symptoms of chronic musculoskeletal pain (Bazzichi et al., 2010; Inanir et al., 2015; Kosek et al., 2016). Sufferers of the condition have been found to possess polymorphisms in catechol-O-methyltransferase (COMT), substance P receptors, dopamine transporters and alpha1-antitrypsin and serotonin transporters. These polymorphisms impact molecular compounds that are responsible for sensory processing and stress response. Possible genetic indicators of fibromyalgia have also been found in autoantibodies, sex hormones, serological and biochemical abnormalities, neuropeptides, proteins, and muscle abnormalities. The biggest difficulty for studies seeking genetic markers for fibromyalgia is that very often subjects suffer comorbidities. It cannot be shown with certainty that a specific marker is associated uniquely with fibromyalgia.

Of the genes implicated in fibromyalgia, those responsible for nociceptive transient receptor potential vanilloid (TRPV) channels have received special attention (Kosek et al.). These genes have also been shown to have pharmacogenetic importance insofar as their variants can impact the effectiveness of drugs aimed at regulating the passage of ions. This article will focus on one of the TRPV family of genes: the TRPV 1 gene.


 * Materials and Methods**
 * Prevalence of Fibromyalgia**
 * TRPV Genes Family Portrait**
 * Imaging the TRPV1 Protein Channel**
 * Broader Impact - Pharmacogenetics and Fibromyalgia**
 * Criticism of the Proove Genetic Test**
 * Discussion - The Genetic Approach to Fibromyalgia**
 * Works Cited - Fibromyalgia**

 Introduction Fibromyalgia designates a condition of chronic musculoskeletal pain that can also include cognitive dysfunction, sleep disorders, and mood swings. It effects about 2% of the population and is most common in middle-aged women. Although there is no certain cause for fibromyalgia, two areas that have been implicated in its etiology are central nervous system nociceptive processing and psychological factors such as stress. In recent times, however, research has uncovered evidence that DNA may hold the key to understanding the etiology of fibromyalgia. Many researchers today are looking for genetic markers of fibromyalgia that might indicate if not a cause than at least a predisposition for the disease. Specific genes have been associated with the pain and symptoms of chronic musculoskeletal pain (Bazzichi, L., et al. 2010, Inanir, A., et al, 2015, Kosek, E, et al., 2016). Sufferers of the condition have been found to possess polymorphisms in catechol-O-methyltransferase (COMT), of substance P receptors, dopamine transporters and alpha1-antitrypsin and serotonin transporters. These polymorphisms impact molecular compounds that are responsible for sensory processing and stress response. Possible genetic indicators of fibromyalgia have also been found in autoantibodies, sex hormones, serological and biochemical abnormalities, neuropeptides, proteins, and muscle abnormalities. The biggest difficulty with the studies seeking genetic markers for fibromyalgia is that very often, subjects suffer comorbidities. It cannot be shown with certainty that a specific marker is associated uniquely with fibromyalgia. Of the genes implicated in fibromyalgia, those responsible for nociceptive transient receptor potential vanilloid (TRPV) channels have pharmacogenetic importance insofar as variants of these genes can impact the effectiveness of drugs aimed at regulating the passage of ions. Cohen, M., et al (2015) established TRPV2 as a critical intracellular ion channel in neuronal function. This study will present current research on TRPV channels and their encoding gene sequences with an eye to how this information will impact pharmacogenomic treatment of fibromyalgia.  Table 1 Prevalence of fibromyalgia in the general population Country Author Case definition N Age range (y) Prevalence (%) Overall Female Male Africa Tunisia Guermazi [9] LFESSQ 1,000 ≥15 9.3 – – Americas Brazil Senna [10] COPCORD 3,038 ≥16 2.5 3.9 0.1 Canada White [11] 1990 ACR 3,395 ≥18 3.3 4.9 1.6 Canada McNally [12] Self-reported 131,535 ≥12 1.1 1.8 0.3 USA Wolfe [13] 1990 ACR 3,006 ≥18 2.2 3.4 0.5 USA Vincent [14•] 2010 ACR 3,410 ≥21 6.4 7.7 4.9 Asia Bangladesh Haq [15] COPCORD 5,211 ≥15 3.6 6.2 0.9 China Scudds [16] 1990 ACR 1,467 – 0.8 – – Israel Ablin [3] LFESSQ + 1990 ACR 1,019 ≥18 2.0 2.8 1.1 Malaysia Veerapen [17] COPCORD 2,594 ≥15 0.9 1.5 0.2 Pakistan Farooqi [18] COPCORD 1,997 ≥15 2.1 – – Thailand Prateepavanich [19] 2010 ACR 1,000 – 0.6 – – Europe Denmark Prescott [20] 1990 ACR 1,219 18–79 0.7 – – France Bannwarth [21] LFESSQ + 1990 ACR 1,014 ≥15 1.4 2.0 0.7 France Perrot [22•] LFESSQ + 1990 ACR 3,081 ≥18 1.6 – – Finland Mäkelä [23] Yunus criteria 7,217 ≥30 0.75 1.0 0.5 Germany Branco [24•] LFESSQ + 1990 ACR 1,002 ≥15 3.2 3.9 2.5 Germany Wolfe [25•] 2010 ACR 2,445 ≥14 2.1 2.4 1.8 Greece Andrianakos [26] 1990 ACR 8,740 ≥19 0.4 – – Italy Salaffi [27] 1990 ACR 2,155 ≥18 2.2 – – Italy Branco [24•] LFESSQ + 1990 ACR 1,000 ≥15 3.7 5.5 1.6 Portugal Branco [24•] LFESSQ + 1990 ACR 500 ≥15 3.6 5.2 1.8 Spain Branco [24•] LFESSQ + 1990 ACR 1,001 ≥15 2.3 3.3 1.3 Spain Mas [28] 1990 ACR 2,192 ≥20 2.4 4.2 0.2 Sweden Lindell [29] 1990 ACR 2,425 20–74 1.3 2.4 0.0 Turkey Turhanoglu [30] 1990 ACR 600 – 8.8 12.5 5.1 Mean 2.7 4.1 1.4 LFESSQ London Fibromyalgia Epidemiology Study Screening Questionnaire; COPCORD Community Oriented Program for the Control of Rheumatic Diseases; ACR American College of Rheumatology 