Corticotropin-releasing hormone promoter polymorphisms in patients with rheumatoid arthritis from northwest Spain.
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).


CONCLUSIONS
In Northwest Spain, polymorphism in the CRH gene regulatory region may play a role as a disease susceptibility marker for late onset seronegative RA.
Divisions of Rheumatology and Endocrinology, Hospital Xeral-Calde, Lugo, Spain.
Miguel A
MA
Gonzalez-Gay
Ali H
AH
Hajeer
Carlos
C
Garcia-Porrua
Adele
A
Dababneh
Mahsa M
MM
Amoli
Manuel A
MA
Botana
Wendy
W
Thomson
Javier
J
Llorca
William E R
WE
Ollier
D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013030:Spain
D005819:Genetic Markers; D003346:Corticotropin-Releasing Hormone