Corticotropin releasing hormone (CRH) promoter polymorphisms in various ethnic groups of patients with rheumatoid arthritis

The regulatory region of the corticotropin releasing hormone (CRH) is highl y conserved and plays a crucial role in the response of the organism to str ess. 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 rel easing hormone (CRH) response to stress in patients with rheumatoid arthrit is (RA) has a genetic basis, we investigated the distribution of CRH allele s in a cohort of UK patients as well as in South African RA patients. Methods: Restriction fragment length polymorphism of PCR amplified DNA prod ucts of the CRH promoter. We compared the allele frequencies in the RA pati ents with the respective healthy control population described previously. Results: As in the control populations we found two biallelic polymorphic s equences (named Al and A2 and B1 and B2, respectively) in the CRH promoter which could be assigned to compound alleles. The A2B1 compound allele was p rotective against development of RA in a large group of UK Caucasoid patien ts (p = 0.03; odds ratio 0.43, 95% confidence interval 0.21-0.88). In contr ast, A1B1 was positively associated with RA in a cohort of black South Afri can 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 furt her genetic and environmental risk factors are determined.