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Open Access Research article

Association between IL-18 gene polymorphisms and biopsy-proven giant cell arteritis

Rogelio J Palomino-Morales1, Tomas R Vazquez-Rodriguez2, Orlando Torres1, Inmaculada C Morado3, Santos Castañeda4, Jose A Miranda-Filloy2, Jose L Callejas-Rubio5, Benjamin Fernandez-Gutierrez3, Miguel A Gonzalez-Gay6 and Javier Martin1*

Author Affiliations

1 Instituto de Parasitología y Biomedicina Lopez-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n Armilla, Granada-18100, Spain

2 Division of Rheumatology, Hospital Xeral-Calde, c/Dr.Ochoa, Lugo 27004, Spain

3 Rheumatology Service, Hospital Clínico San Carlos, c/Profesor Martín Lagos, S/N Madrid - 28040, Spain

4 Department of Rheumatology, Hospital de la Princesa, Universidad Autónoma, c/Diego de León 62, Madrid, 28006, Spain

5 Department of Internal Medicine, Hospital Clínico San Cecílio, Avenida Doctor Olóriz 16 Granada 18012, Spain

6 Division of Rheumatology, Hospital Universitario Marques de Valdecilla, Santander-39008, Spain

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Arthritis Research & Therapy 2010, 12:R51  doi:10.1186/ar2962


See related editorial by Cronstein, http://arthritis-research.com/content/12/4/134

Published: 23 March 2010

Abstract

Introduction

The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis (GCA).

Methods

In total, 212 patients diagnosed with biopsy-proven GCA were included in this study. DNA from patients and matched controls was obtained from peripheral blood. Samples were genotyped for the IL18-137 G>C (rs187238), the IL18-607 C>A (rs1946518), and the IL18-1297 T>C (rs360719) gene polymorphisms with polymerase chain reaction, by using a predesigned TaqMan allele discrimination assay.

Results

No significant association between the IL18-137 G>C polymorphism and GCA was found. However, the IL18 -607 allele A was significantly increased in GCA patients compared with controls (47.8% versus 40.9% in patients and controls respectively; P = 0.02; OR, 1.32; 95% CI, 1.04 to 1.69). It was due to an increased frequency of homozygosity for the IL18 -607 A/A genotype in patients with GCA (20.4%) compared with controls (13.4%) (IL18 -607 A/A versus IL18 -607 A/C plus IL18 -607 C/C genotypes: P = 0.04; OR, 1.59; 95% CI, 1.02 to 2.46). Also, the IL18-1297 allele C was significantly increased in GCA patients (30.7%) compared with controls (23.0%) (P = 0.003; OR, 1.48; 95% CI, 1.13 to 1.95). In this regard, an increased susceptibility to GCA was observed in individuals carrying the IL18-1297 C/C or the IL18-1297 C/T genotypes compared with those carrying the IL18-1297 T/T genotype (IL18-1297 C/C plus IL18-1297 T/C versus IL18-1297 T/T genotype in GCA patients compared with controls: P = 0.005; OR, 1.61; 95% CI, 1.15 to 2.25). We also found an additive effect of the IL18 -1297 and -607 polymorphisms with TLR4 Asp299Gly polymorphism. The OR for GCA was 1.95 for combinations of genotypes with one or two risk alleles, whereas carriers of three or more risk alleles have an OR of 3.7.

Conclusions

Our results show for the first time an implication of IL18 gene-promoter polymorphisms in the susceptibility to biopsy-proven GCA. In addition, an additive effect between the associated IL18 and TLR4 genetic variants was observed.