TNF-α promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritis

• Published in: Scandinavian journal of rheumatology 2005-11, Vol.34 (6), p.451-454
• Main Authors: Modesto, C., Patiño-García, A., Sotillo-Piñeiro, E., Merino, J., García-Consuegra, J., Merino, R., Rua, M. J., Sierrasesúmaga, L., Arnal, C.
• Format: Article
• Language: English
• Subjects: Arthritis, Juvenile - ethnology; Arthritis, Juvenile - genetics; Biological and medical sciences; Child; Confidence Intervals; Diseases of the osteoarticular system; Gene Frequency - genetics; Genetic Predisposition to Disease; Humans; Inflammatory joint diseases; Medical sciences; Odds Ratio; Polymorphism, Genetic; Promoter Regions, Genetic; Spain - ethnology; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0300-9742; 1502-7732
• DOI: 10.1080/03009740510026652

Objective: To explore the possible association/s of the first reported tumour necrosis factor (TNF-αTNF-) α promoter gene polymorphisms −308, −238, −376 and −163 (G→A) with systemic (SoJIA) and oligoarticular subtypes of juvenile idiopathic arthritis (JIA); and to test the association between these polymorphisms and the class I/class II HLA alleles in our population. Methods: The patient group comprised 29 oligoarticular and 26 systemic Caucasian Spanish children with JIA; 68 healthy volunteers from the same ethnic group and geographical region served as controls. HLA alleles were determined using low-resolution polymerase chain reaction (PCR). TNF-α promoter gene polymorphisms were screened using PCR denaturing gradient gel electrophoresis (PCR-DGGE), followed, if positive, by restriction fragment length polymorphism (RFLP) analysis for identification. Results: No statistical association was found between the four polymorphisms studied and JIA. However, the −308 G→A polymorphism (TNF A2) tended to be more frequent in patients with SoJIA than in the oligoarticular group. TNF A2 was strongly associated with the extended haplotype A1B8DR3 (p = 0.003), and the tandem polymorphism −238/−376 in the presence of B18 and DR3. Conclusion: The TNF A2 allele was more frequent in SoJIA than in the oligoarticular group. TNF A2 can help to create a more inflammatory milieu in this JIA subtype, in combination with other polymorphisms involved in regulatory sequences of key molecules in the inflammatory response. The association of the −308 and −238/−376 polymorphisms with specific alleles of the HLA is reconfirmed.