Rheumatology Advance Access published online on June 29, 2004
Rheumatology, doi:10.1093/rheumatology/keh283
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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1 Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain
* To whom correspondence should be addressed. E-mail: miguelaggay{at}hotmail.com.
Objective. To assess the influence of inducible and endothelial nitric oxide synthase (iNOS and eNOS) polymorphisms in susceptibility to rheumatoid arthritis (RA). Methods. Two hundred RA patients fulfilling the 1987 American College of Rheumatology classification criteria followed at the out-patient rheumatology clinic of the Hospital Xeral-Calde (Lugo, Spain) and 251 ethnically matched controls were studied. Patients and controls were genotyped by PCR-based techniques for a multiallelic (CCTTT)n repeat in the promoter region of the iNOS gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. Results. No significant difference in allele or genotype frequencies for either polymorphism in the eNOS gene was observed between RA patients and controls. The overall iNOS CCTTTn allelic or genotypic distribution did not show statistical significant differences between RA patients and controls. Interestingly, when we stratified the iNOS alleles into short (8-11) and long (12-16) repeats, significant differences were observed between RA patients and controls (P = 0.021; odds ratio = 1.37, 95% confidence interval 1.04-1.81). Of note, individuals carrying two alleles with a repeat number less than 12 (fewer than 196 base pairs) exhibited a double risk of developing RA (P = 0.005, odds ratio 2.26, 95% confidence interval 1.25-4.08). Conclusions. Significant differences in the iNOS promoter polymorphism genotype frequency between northwest Spanish RA patients and controls suggest a potential role for this polymorphism in susceptibility to RA.
Accepted May 28, 2004
Original Papers
Inducible but not endothelial nitric oxide synthase polymorphism is associated with susceptibility to rheumatoid arthritis in northwest Spain
2 Division of Preventive Medicine and Public Health, School of Medicine, University of Cantabria, Santander, Spain
3 Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, Spain
4 Division of Immunology, Hospital Virgen de las Nieves, Granada, Spain
5 Centre for Integrated Genomic Medical Research, School of Epidemiology and Health Sciences, University of Manchester, Manchester, UK
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Abstract
Drs Gonzalez-Gay and Martin share senior authorship in this study.
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