ab2002

Corticotropin releasing hormone promoter polymorphisms in giant cell arteritis and polymyalgia rheumatica

M.A. Gonzalez-Gay¹, A.H. Hajeer², A. Dababneh³, C. Garcia-Porrua¹, M.M. Amoli³, W. Thomson³, W.E.R. Ollier³

¹Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain; ²Department of Pathology and Laboratory Medicine, King Fahad National Guard Hospital, Kingdom of Saudi Arabia; and ³ARC Epidemiology Unit, Manchester University Medical School, Manchester, United Kingdom

ABSTRACT
Objective
Giant cell (temporal) arteritis (GCA) and polymyalgia rheumatica (PMR) are different but overlapping diseases of unknown etiology affecting the elderly. Corticotropin-releasing hormone (CRH) helps to regulate the immune response and maintain homeostasis during inflammatory stress. CRH promoter region polymorphisms in the 5' regulatory region of the CRH gene have been described. To investigate the possible implications of the CRH promoter polymorphisms in PMR and GCA susceptibility we have examined a series of patients with these conditions.

Methods
Sixty-two patients with biopsy-proven GCA, 86 patients with isolated PMR and 147 ethnically matched controls from the Lugo region of Northwest Spain were included in this study. Patients and controls were genotyped for CRH polymorphism in the 5' regulatory region of the gene at position 1273 (alleles A1 and A2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Allele frequencies and genotype distribution were evaluated by the chi-square test.

Results
When GCA and PMR patients were examined for alleles and genotypes for each CRH polymorphism no significant differences in frequency were found compared with controls. A higher CRH-A2 allele frequency was observed in GCA patients with visual complications (21.4%) compared with controls (9.2%) and GCA cases without eye involvement [6.3%; p= 0.017, p_corr = 0.034, O.R: 4.1 (95% CI 1.2- 13.9)], although this was based on a small sample of patients with ischemic visual complications (n = 14) and should be interpreted with caution. No differences in CRH allele or genotype frequencies were observed in isolated PMR patients stratified by relapses and recurrence of disease symptoms.

Conclusion
Polymorphisms in the CRH gene regulatory region do not appear to be associated with increased susceptibility to PMR or GCA. The CRH-A2 allele may encode risk for the development of visual complications in GCA, although further studies to confirm this will be required.

Key words
Giant cell (temporal) arteritis, polymyalgia rheumatica, CRH, disease susceptibility, visual complications.

Please address correspondence to: Miguel A. Gonzalez-Gay, MD, PhD, Rheumatology Division. Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004 Lugo, Spain. E-mail: miguelaggay@hotmail.com