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Fibromyalgia gene discovery: High proportion of patients carry one copy of mutation affecting inflammatory response, brain development

  [ 145 votes ]   [ 1 Comment ]
www.ProHealth.com • March 21, 2012


Article:
Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are not always silent
– Source: NeuroToxicology, Mar 10, 2012

By Donald E Schmechel, Christopher Edwards

[Note: Alpha-1 Antitrypsin (ATT) is an anti-inflammatory produced by the liver mainly to protect the lungs. People with 2 copies of a gene mutation linked to abnormal ATT often develop liver and lung disease (e.g., COPD, emphysema).

People with a single copy of the mutation may be ‘silent’ carriers or exhibit 'intense' creative energy. Now this large-population study at Duke finds the single copy is highly associated with fibromyalgia and widespread pain disorder (in 38% of cases), ADD, PTSD, and more – all suggesting the polymorphisms' role in abnormalities of brain development and inflammatory response. For more information see the Alpha-1 Foundation Website.

The research further suggests that genotyping can identify high-risk and low-risk fibromyalgia subsets.] 

Abstract:
Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers." Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE") - associated with A1AT polymorphisms.

We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients.

This is a retrospective case control series of 3,176 consecutive patients presenting to: Duke University Memory Clinic (747 patients), and to regional community-based Caldwell Hospital Neurology and Memory center (2,429 patients).

Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses.

• Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications.

• Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%).

• Presence of chronic widespread pain or FMS was common (14%-22%) with average age at presentation of 56 years old and mostly female gender (82%).

• Patients with chronic widespread pain/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%).

• Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype.

• Significant reductions in chronic widespread pain/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes.

• Since intense creative energy (ICE) phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response.

• In support of this concept is finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms (63%), suggesting a spectrum for JRA to later FMS presentations.

• Likewise, persons reporting a history of attention deficit disorder (ADD) had an increased proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%).

• Toxic environmental exposures are common (23%) and associated with diagnoses of PSP, PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic exposure and PSP, PPA and FTD-PD.

Our findings support the intense creative energy behavioral phenotype for A1AT polymorphism carriers and the reported association with anxiety and bipolar spectrum disorders.

We now extend that phenotype to apparent vulnerability to inflammatory muscle disease in a spectrum from juvenile rheumatoid arthritis (JRA) to fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific late onset neurological syndromes (FTD-PD and PPA) [fronto-temporal dementia, Parkinson's disease, primary progressive aphasia].

High and low risk FMS subsets can be defined using A1AT, MTHFR and APOE genotyping.

Clinical diagnoses associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer Disease subtypes.

These results support an extended phenotype for A1AT mutation carriers beyond liver and lung vulnerability to:

• Selective advantages: ICE phenotype

• And disadvantages: fibromyalgia, affective disorders, and selected late onset neurological syndromes.

Source: NeuroToxicology, Mar 10, 2012. Schmechel DE, Edwards C. The Falls Neurological and Memory Center, Caldwell Memorial Physician Network, Granite Falls, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. [Email: don.schmechel@gmail.com]




Please Discuss This Article:   Post a Comment 

ICE and Fibromyalgia, Pain, etc..
Posted by: 1peekaboo
May 17, 2012
I thought this research and concept were very interesting. Looking back, my most severe symptoms of Fibro also corresponded with an increased talent in art, moreso than I had ever had in my youth...at age 30 when I had my son, 1 year later I was creating artworks that I had not been able to create earlier. (Although I was always "crafty and artistic".

The pain that I have endured since my son's birth in 1990, and my daughter in 1993, has been much more severe than what i experienced from age 18 to 29. Although I did have significant fatigue and pain, and difficulty working. My Mother exhibits the same symptoms, and at age 79, has mild to moderate Dementia. I am finding myself increasingly unable to perform physical tasks like housework and gardening, and easily tired by recreational sports (example: I played 6 games of pool on Monday, two days later my right arm was in severe pain all day with cramping, in spite of my medications).

I have an extremely low tolerance to pain, and wonder if I should have a Med Alert Bracelet....because I take Morphine, Klonopin, Neurontin, and Prozac. If I were to be in an accident i think the shock of the pain might kill me unless the right amount of pain meds were given. Do you Agree?

I would like to offer myself available for interviews or trials. I am 51 years old, and I am, your classic case of Fibro. I have all the usual causative factors, and most of the resulting conditions. I would like to know what I can expect in the future, and I want to learn as much as I can for my kids, in case they might be affected.

I was very interested in your article and will continue to follow your research, as I also continue to do my own.

Thank you!
Diane
Reply Reply
 
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