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Identification of Differential Genetic Profiles in Severe Forms of Fibromyalgia and Chronic Fatigue Syndrome – Source: Report presented at 2007 IACFS/ME conference in Fort Lauderdale, FL

  [ 5 votes ]   [ Discuss This Article ]
By FJ Garcia-Fructuoso, et al. • • December 20, 2007

Fibromyalgia (FMS) and Chronic Fatigue Syndrome (CFS) are two controversial diseases with overlapping symptoms, difficult to distinguish and diagnose properly.1,2 To date there are no biological markers for either condition and [they] are diagnosed using separate but overlapping clinical criteria. All too often the patients’ concerns are dismissed as imaginary or unimportant and only recently they have started to be recognized and accepted by physicians.

The severity of both diseases varies according to patient, and it affects the prognosis and the therapeutic approach with important consequences for the individual's quality of life.3

Therefore it is necessary to distinguish between the subtypes. Since recent studies have started to point out the genetic background of these diseases we suggested the use of SNP analysis to investigate their different genetic profiles. [SNP stands for ‘single nucleotide polymorphisms’, which are DNA sequence variations that occur when a single nucleotide in the genome sequence is changed.] Among the individuals registered in the “Fibromyalgia and/or Chronic Fatigue Syndrome Patients Record" ( [a foundation-sponsored registry for patients who are Spanish and/or residents of Spain], 1,500 subjects diagnosed with FM, CFS or both were randomly selected and invited to participate in the study. From these, 1,371 gave written consent to take part and filled in a questionnaire which included details about their diagnosis, familiar diagnosis of FM or CFS, and presence of mental disorders.

In addition, those patients were also asked to answer the FIQ [Fibromyalgia Impact Questionnaire]4 and the CSI [CDC Symptom Inventory] for CFS5 and to provide a blood sample for DNA extraction.

Taking into account that there is a recognized gender bias in FIQ, eventually only women were included in the study. Previous treatment for psychiatric disorders was also considered an exclusion criterion.

At the end of the selection process the number of recruited subjects was reduced to 403 patients (186 FM patients aged 45-54 years and 217 CFS patients aged 30-39 years). These cases were clinically diagnosed according to the 1990 American College of Rheumatology (ACR) classification for FM6 or the U.S. Centers for Disease Control criteria for CFS developed by Fukuda et al.7 at the Hospital Clinic and Clinica CIMA (Barcelona, Spain).

For each sample 107 SNPs were genotyped by SNPlexTM. An independent second association study with 282 women (126 FM / 156 CFS) was used to validate the results.

We identified 15 SNPs able to discriminate between FM and CFS patients with a 11.5 Likelihood Ratio (LR+, 95% specificity). [Likelihood Ratios greater than 10 are considered “convincingly good.’] The analysis of further SNPs allowed differential genetic profiling between the most aggressive FM phenotype and the mild forms (12.4 LR+) and between a severe CFS phenotype and a milder one (12.4 LR+).

In this study we prove that genetic profiling via SNP analysis can be a very effective tool to discriminate between the more severe FM and CFS cases. In addition we claim that FM and CFS are two separate diseases with an important genetic component, and we suggest that the severe cases might be different disease subtypes with distinctive genetic profiles.

However this methodology is still depend[dent on] a preliminary reliable diagnosis that fulfills all the disease inclusion and exclusion criteria.

Source: Article presented at January 2007 IACFS/ME Conference, Ft. Lauderdale, Florida. By Olano-Martin E, Lao-Villadoniga JI, Santos C, Poca-Dias V, Fernandez-Sola J, Martinez A, Simon L, Tejedor D, Garcia-Fructuoso FJ. ClMA Clinic Department of Rheumatology [Barcelona, Spain]; Laboratorio Dr. Echevame, Molecular Genetics Department; Progenika Biopharma, SA; University of the Azores (Portugal), Department of Biology (CIRN); Hospital Clinic, Chronic Fatigue Unit [Barcelona]; Asociacion Genica para el Desarrollo de la Genomica y Proteomica.

[Note: ProHealth published a different abstract of this research in May 2007 that was issued in conjunction with the authors’ presentation at the June 2007 European Congress of Rheumatology in Barcelona.]

1. Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ. The specificity of the CDC-I994 criteria for chronic fatigue syndrome: Comparison of health status in three groups of patients who fulfill the criteria. Ann Epidemiol 2004;14(2):95-100.

2. Birtane M, Uzunca K, Tastekin N, Tuna H. The evaluation of quality of life in Fibromyalgia syndrome: A comparison with rheumatoid arthritis by using SF-36 Health Survey. Clin Rheumatol 2007; 26(5):679-684. 3. Buchwald D. Fibromyalgia and chronic fatigue syndromes: Similarities and differences. Rheum Dis Clin North Am 1996; 22(2):219-243. 4. Burckhard CtS, Clark SR, Bennet RM, The Fibromyalgia impact questionnaire: Development and validation. J. Rheumatol 1991; 18(5):728-733. 5. Wagner D, Nisenbaum R, Heim C, Jones JF, Unger ER, Reeves WC. Psychometric properties of the CDC Symptom lnventory for assessment of chronic fatigue syndrome. Popul Health Metr 2OO5; 3:8. 6. Wolfe F, Smythe HA, Yunus MB, et al, The American College of Rheumatology 1990 Criteria for the classification of Fibrornyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990; 33(2):160-172. 7. Fukuda K , Straus SE, Hickie l, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: A comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann lntem Med 1994;121(12):953-959.

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