In an allied review I have discussed the evolving role of epigenetics as the valued mechanism for explaining how gene expression rather than DNA change determines and mediates risk for complex health problems. In addition epigenetics helps to explain cross generational exposure transmission and why despite their being less than 1% variation in human DNA between individuals they can experience significant differences in health and function.
Great hopes were pinned on the discovery of our DNA yet as discussed in a related post we have less DNA than a grape and certainly less than was originally thought, just slightly more than a humble fruit fly in fact – so surely DNA cannot carry all of our aspirations and risk within that elegant double helix.
So far only a few meagre discoveries (albeit terrific for the relevant patients) have met the initial expectations. In large this may be attributed to the somewhat fundamental flaw that genes do not exist in isolation but are surrounded by the terrestrial and biological soup referred to as the ‘environment’. This combination of interactions makes a very unlikely setting for science to discover monogenic explanations for common diseases.
Two diseases of the musculoskeletal system and other tissues describe quite elegantly the relevance of an external bacterial agent to a genetic susceptibility before a disease process is initiated.
Ankylosisng spondylitis (AS)
It is estimated that the histocompatibility antigen HL-A B27 is present in up to 96% of patients with AS whilst as little as 8% of the AS free population have it.[1] Presence of the gene does not predict symptomatology as only 10-20% of these individuals display some of the symptoms of AS such as morning back stiffness and general backache, the majority are symptom free.
It takes the molecular interaction between this gene and the gastrointestinal organism klebsiella pneumonia to initiate the disease process. Whilst there remain some questions about the validity of this association[2] one study found antibodies to this organism in AS patients from 14 differing countries.[3] The genetic risk from HL-A B27 is less relevant than the association between the gene and a bacterium found in the intestines, supporting the infection/environment interaction to induce suitable epigenetic expressions.
Rheumatoid Arthritis (RA)
A somewhat similar process is found in RA, here 90% of patients share the the same epitope (A localised region on the surface of an antigen that is capable of eliciting an immune response and of combining with a specific antibody to counter that response.) described as (EQRRAA) found in the gene HL-A-DR1/4 whilst the unaffected portion of the population has a frequency occurrence of just 30%.[4]
Here the organism Proteus haemolysin shares the epitope and the gene sequence ESRRAL and clinically, RA patients, particularly those with active disease, have somewhat higher titres of antibodies to Proteus than controls.[5]
Genes related to RA are best expressed – if that is not an oxymoron, when activated by an environmental factor such as that provided following an upper urinary tract infection by the Proteus bacteria. Reliance solely on genes as indicators of disease risk and progression independent of the epigenetic intervention would be to miss the elephant in the room.[6]
Comment
The role of diet on gene expression is understood to be significant, even in a few weeks of suitable changes there can be dramatic changes in the expression of complex diseases including autoimmune diseases. There is a common link here between the health of the wet surfaces of our bodies – the mucosal tissues and risk. The nutritional therapist has a powerful role to play in guiding their patient through nutritional and supplemental strategies to restore wet barrier function, improve immune tolerance and support the eradication of identified pathogens whilst managing the remaining healthy microorganisms.
References
[1] Al-Rawi ZS, Al-Shakarchi HA, Hasan F, Thewaini AJ. Ankylosing spondylitis and its association with the histocompatibility antigen HL-A B27: an epidemiological and clinical study. Rheumatol Rehabil. 1978 May;17(2):72-5. View Abstract
[2] Stone MA, Payne U, Schentag C, Rahman P, Pacheco-Tena C, Inman RD. Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis. Rheumatology (Oxford). 2004 Feb;43(2):148-55. Epub 2003 Aug 29. View Paper
[3] Rashid T, Ebringer A, Wilson C, Bansal S, Paimela L, Binder A. The potential use of antibacterial peptide antibody indices in the diagnosis of rheumatoid arthritis and ankylosing spondylitis. J Clin Rheumatol. 2006 Feb;12(1):11-6 View Abstract
[4] Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987 Nov;30(11):1205-13. Review
[5] Ebringer A, Ptaszynska T, Corbett M, Wilson C, Macafee Y, Avakian H, Baron P, James DC. Antibodies to proteus in rheumatoid arthritis. Lancet. 1985 Aug 10;2(8450):305-7. View Abstract
[6] Adams DD, Knight JG, & Ebringer A (2010). Autoimmune diseases: Solution of the environmental, immunological and genetic components with principles for immunotherapy and transplantation. Autoimmunity reviews, 9 (8), 525-30 PMID: 20083235
