Public Release:  Genetic pathway responsible for link between body clock disturbance and worsening arthritis

European League Against Rheumatism

Copenhagen, Denmark, Wednesday 10 June 2009: The genes that regulate human circadian rhythm, or 'the body clock', are significantly disturbed in individuals with arthritis, according to the results of a new study presented today at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark. Notably, a specific genetic pathway has been identified as responsible for interactions between the genes that regulate the body clock and those that may worsen symptoms of arthritis.

In a sample of 200 rheumatoid arthritis (RA) patients, sleep was determined to be significantly disturbed in over 61%, as determined by a Pittsburg Sleep Quality Index (PSQI) score of >5 (the PSQI global score was 8.55 ±4.69). These values were shown to correlate with several measures of arthritis disease activity, including levels of c-reactive protein, swollen joint count and DAS28*.

A further element of the study looked into the expression patterns of certain genes in mice with arthritis. Here, researchers identified a novel biochemical pathway in which the circadian regulatory gene CRY was found to up-regulate expression of a gene which promotes the activation of TNF-alpha (tumour necrosis factor-alpha, a pro-inflammatory cytokine used by the body to boost the immune system) by two fold, when comparing mice with the CRY gene removed to those with a normal copy of the gene.

Professor Shunichi Shiozawa of Kobe University Graduate School of Medicine and University Hospital, Japan, who led the research said: "Our study has shown that arthritis interferes with the genetics behind an individual's circadian rhythm and, specifically, that certain body clock genes may play a part in the activation of TNF-alpha, a signaling molecule that has an important role in the inflammation commonly seen in a number of rheumatologic conditions. The identification of this curious pathway may help to explain the 24-hour symptom cycle seen by many patients who experience worsening of joint pain and stiffness in the mornings, and lead to further research into new approaches for improving daily quality of life."

RA patients who participated in the study were attending the Kakogawa Konan Hospital and Kobe University Hospitals. Experimental arthritis was induced in mice with the CRY gene removed. Expression of the genes responsible for regulation of the human body clock were determined by immunohistochemistry and quantitative Polymerase Chain Reaction. TNF-alpha levels were measured by ELISA, and transactivation of TNF-alpha gene was examined by reporter assay.

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* DAS28 (Disease Activity Score) is an index used by physicians to measure how active an individual's RA is. It assesses number of tender and swollen joints (out of a total of 28), the erythrocyte sedimentation rate (ESR, a blood marker of inflammation), and the patient's 'global assessment of global health'. A higher score indicates more active disease.

For further information on this study, or to request an interview with the study lead, please do not hesitate to contact the EULAR congress press office on:
Email: eularpressoffice@uk.cohnwolfe.com
Rory Berrie: Onsite tel: +44 (0) 7894 386 425
Camilla Dormer: Onsite tel: +44 (0) 7876 190 439
Abstract number: AB0084

About EULAR

The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

In line with The European Union of Medical Specialists (UEMS), EULAR defines rheumatology as including rheumatic diseases of the connective tissue, locomotor and musculoskeletal systems.

The aims of EULAR are to stimulate, promote, and support the research, prevention, treatment and rehabilitation of rheumatic diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with rheumatic diseases.

In 2009, The EULAR Executive Committee launched the EULAR Orphan Disease Programme (ODP) which aims to provide funding to research programmes focused on furthering understanding of the disease mechanisms behind systemic sclerosis. Please see www.eular.org for further information.

Diseases of the bone and joints such as rheumatoid arthritis and osteoarthritis cause disability in 4-5% of the adult population and are predicted to rise as people live longer.

As new treatments emerge and cellular mechanisms are discovered, EULAR 2009 is set to be the biggest rheumatology event in Europe with over 13,500 scientists, physicians, allied health professionals, and related audiences in attendance from over 100 countries. Over the course of the congress, more than 300 oral and 1700 poster abstract presentations will be featured, with 780 invited speaker lectures taking place in more than 150 sessions.

To find out more about the activities of EULAR, visit: www.eular.org

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