Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The regulatory region of the corticotropin releasing hormone (CRH) is highly conserved and plays a crucial role in the response of the organism to stress. Release of CRH initiates a cascade of events leading to the release of cortisone and the regulation of inflammatory and immune events. OBJECTIVE: Since it has been postulated that the impaired corticotropin releasing hormone (CRH) response to stress in patients with rheumatoid arthritis (RA) has a genetic basis, we investigated the distribution of CRH alleles in a cohort of UK patients as well as in South African RA patients. METHODS: Restriction fragment length polymorphism of PCR amplified DNA products of the CRH promoter. We compared the allele frequencies in the RA patients with the respective healthy control population described previously. RESULTS: As in the control populations we found two biallelic polymorphic sequences (named A1 and A2 and B1 and B2, respectively) in the CRH promoter which could be assigned to compound alleles. The A2B1 compound allele was protective against development of RA in a large group of UK Caucasoid patients (p = 0.03; odds ratio 0.43, 95% confidence interval 0.21-0.88). In contrast, A1B1 was positively associated with RA in a cohort of black South African RA patients (p = 0.05; odds ratio 1.78, 95% confidence interval 1.01-3.15). CONCLUSION: Taken together, these findings support the hypothesis that CRH promoter polymorphism represents a new genetic marker for RA susceptibility and may prove useful for the prediction of RA risk in the future when further genetic and environmental risk factors are determined.

Original publication

DOI

10.1007/s003930050002

Type

Journal article

Journal

Zeitschrift fur Rheumatologie

Publication Date

02/2000

Volume

59

Pages

29 - 34

Addresses

Molecular Immunogenetics and Rheumatology Units, United Medical and Dental Schools, Guy's Hospital, London, United Kingdom. baec@medizin.uni-leipzig.de

Keywords

Humans, Arthritis, Rheumatoid, Corticotropin-Releasing Hormone, HLA-DR4 Antigen, Cohort Studies, Polymerase Chain Reaction, Genetics, Population, Gene Frequency, Genotype, Polymorphism, Restriction Fragment Length, Alleles, Reference Values, Adult, Middle Aged, African Continental Ancestry Group, Asian Continental Ancestry Group, European Continental Ancestry Group, South Africa, Hong Kong, England, Female, Male, Promoter Regions, Genetic