Corticotropin-Releasing Hormone Promoter Polymorphisms in Patients with Rheumatoid Arthritis from Northwest Spain

MIGUEL A. GONZALEZ-GAY, ALI H. HAJEER, CARLOS GARCIA-PORRUA, ADELE DABABNEH, MAHSA M. AMOLI, MANUEL A. BOTANA, WENDY THOMSON, JAVIER LLORCA, and WILLIAM E.R. OLLIER

ABSTRACT.

Objective. To investigate the possible implications of polymorphism in the CRH promoter in rheumatoid arthritis (RA) susceptibility, we examined a series of patients with RA from a defined area of Northwest Spain.

Methods. A total of 177 patients with RA and 147 ethnically matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for CRH polymorphisms 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. Patients were stratified for age at onset of disease and rheumatoid factor status.

Results. When the whole group of patients was examined, no significant differences in CRH allele or genotype frequency were found compared with controls. However, the CRH allele A2 was significantly increased in patients with late onset seronegative RA compared with the seronegative group with younger age of disease onset (p = 0.03). In addition, 4 (36.4%) of the 11 patients with late onset seronegative RA carried the CRH-A2 allele versus only 2 (6.6%) of 31 patients with seronegative RA beginning before age 61 (OR 8.3, 95% CI 1.4–47.0; p = 0.015).

Conclusion. In Northwest Spain, polymorphism in the CRH gene regulatory region may play a role as a disease susceptibility marker for late onset seronegative RA. (J Rheumatol 2003;30:913-7)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
AGE OF ONSET
RHEUMATOID FACTOR
DISEASE SUSCEPTIBILITY
CRH

From the Divisions of Rheumatology and Endocrinology, Hospital Xeral-Calde, Lugo, Spain; Division of Preventive Medicine and Public Health, School of Medicine, University of Cantabria, Santander, Spain; and Centre for Integrated Genomic Medical Research, School of Epidemiology and Health Sciences, University of Manchester, Manchester, United Kingdom.

M.A. Gonzalez-Gay, MD, PhD; C. Garcia-Porrua, MD, PhD, Rheumatology Division; M.A. Botana, MD, PhD, Endocrinology Division, Hospital Xeral-Calde; J. Llorca, MD, PhD, Division of Preventive Medicine and Public Health, School of Medicine, University of Cantabria; A.H. Hajeer, PhD; A. Dababneh, PhD; M.M. Amoli, MD; W. Thomson PhD; W.E.R. Ollier, PhD, FRCPath, Centre for Integrated Genomic Medical Research, School of Epidemiology and Health Sciences, University of Manchester.

Address reprint requests to Dr. M.A. Gonzalez-Gay, Rheumatology Division, Hospital Xeral-Calde, c/ Dr. Ochoa s/n, 27004 Lugo, Spain.

Submitted March 1, 2002; revision accepted November 27, 2002.

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