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Inducible Nitric Oxide Synthase Polymorphism Is Associated with Susceptibility to Henoch-Schönlein Purpura in Northwestern Spain
JAVIER MARTIN, LAURA PACO, MARIA P. RUIZ, MIGUEL A. LOPEZ-NEVOT, CARLOS GARCIA-PORRUA, MAHSA M. AMOLI, MARIA C. CALVIÑO, WILLIAM E.R. OLLIER, and MIGUEL A. GONZALEZ-GAY
ABSTRACT.
Objective. To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to the susceptibility to Henoch-Schönlein purpura (HSP), and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae). Methods. Fifty-eight patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n = 251) were genotyped by PCR based techniques for a multiallelic (CCTTT)n and for the biallelic TAAA repeat in the promoter region of the NOS2A gene. Results. HSP patients exhibited a significantly increased frequency of the NOS2A short (8– 11) CCTTTn alleles (OR 1.64, 95% CI 1.09– 2.47, p = 0.017) and genotypes (OR 3.59, 95% CI 1.79– 7.20, p = 0.0002) compared to controls, particularly when patients with nephritis were compared with controls. However, when the NOS2A TAAA repeat polymorphism was assessed, no differences were found. Conclusion. Significant differences in the NOS2A promoter polymorphism allele and genotype frequency between HSP patients and controls suggest a potential role for this gene in the susceptibility to HSP and in the development of nephritis. (J Rheumatol 2005;32:1081-5) Key Indexing Terms:
HENOCH-SCHÖNLEIN PURPURA
From the Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada; Division of Immunology, Hospital Virgen de las Nieves, Granada; Centre for Integrated Genomic Medical Research, Manchester, UK; and the Divisions of Rheumatology and Pediatrics, Hospital Xeral-Calde, Lugo, Spain. J. Martin, MD, PhD; M.P. Ruiz, BSc, Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC; L. Paco, MD; M.A. Lopez-Nevot, MD, PhD, Division of Immunology, Hospital Virgen de las Nieves; M.M. Amoli, MD, PhD; W.E.R. Ollier, PhD, FRCPath, Centre for Integrated Genomic Medical Research, University of Manchester; M.C. Calviño, MD, Pediatrics Division; C. Garcia-Porrua, MD, PhD; M.A. Gonzalez-Gay, MD, PhD, Rheumatology Division, Hospital Xeral-Calde. Dr. Gonzalez-Gay and Dr. Martin share senior authorship in this study. Address reprint requests to Dr. M.A. Gonzalez-Gay, Rheumatology Division, Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004 Lugo, Spain. E-mail: miguelaggay@hotmail.com Accepted for publication January 27, 2005. |