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Association of a Functional Inducible Nitric Oxide Synthase Promoter Variant with Susceptibility to Biopsy-Proven Giant Cell Arteritis
MIGUEL A. GONZALEZ-GAY, JAVIER OLIVER, ELENA SANCHEZ, CARLOS GARCIA-PORRUA, LAURA PACO, MIGUEL A. LOPEZ-NEVOT, WILLIAM E.R. OLLIER, and JAVIER MARTIN
ABSTRACT.
Objective. To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to susceptibility to giant cell arteritis (GCA). Methods. One hundred three patients with biopsy-proven GCA and 198 ethnically matched controls from the Lugo region (Northwest Spain) were studied. Patients and controls were genotyped using polymerase chain reaction techniques for a multiallelic (CCTTT)n and for the TAAA repeat polymorphism in the promoter region of the NOS2A gene. Results. No significant differences in allele or genotype frequencies for the (CCTTT)n repeat polymorphism in the NOS2A gene between patients with GCA and controls were observed. However, significant differences for the TAAA repeat polymorphism between patients and controls were found. The overall distribution of NOS2A TAAA genotypes in patients with biopsy-proven GCA was significantly different than controls (p = 0.026). Patients with GCA had an increased frequency of the NOS2A TAAA+ allele (16.5%) compared with controls (9.1%) (p = 0.007; OR 1.98; 95% CI 1.20–3.27). This was due to an increased frequency of both heterozygotes (27.2%) and homozygotes (2.9%) for NOS2A TAAA+ observed in patients compared to controls (15.2% and 1.5%, respectively) (p = 0.007; OR 2.15; 95% CI 1.23–3.78). Conclusion. Our results suggest a potential implication for NOS2A TAAA gene polymorphism in GCA susceptibility. (J Rheumatol 2005;32:2178-82) Key Indexing Terms:
GIANT CELL (TEMPORAL) ARTERITIS
From the Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC; Division of Immunology, Hospital Virgen de las Nieves, Granada; Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain; and the Centre for Integrated Genomic Medical Research, Manchester, UK. Supported by grant SAF03-3460 from Plan Nacional de I+D+I and in part by Junta de Andalucía, grupo CTS-180. M.A. Gonzalez-Gay, MD, PhD; C. Garcia-Porrua, MD, PhD, Rheumatology Division, Hospital Xeral-Calde; J. Martin, MD, PhD; J. Oliver, PhD; E. Sanchez, PhD, Instituto de Parasitologia y Biomedicina Lopez-Neyra; M.A. Lopez-Nevot, MD, PhD; L. Paco, PhD, Division of Immunology, Hospital Virgen de las Nieves; W.E.R. Ollier, PhD, Centre for Integrated Genomic Medical Research. Dr. Gonzalez-Gay and Dr. Martin share senior authorship of this report. Address reprint requests to Dr. J. Martin, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain. E-mail: martin@ipb.csic.es Accepted for publication June 20, 2005. |