POSTER NO: 459

TNF-alpha promoter polymorphism in Mexican patients with spondyloarthropathies

¹Gilberto Vargas-Alarcón, ¹Guadalupe Hernández-Pacheco, ¹José Manuel Rodríguez-Pérez, ¹Nonanzit Pérez-Hernández, ²John Londoño, ²Julio Granados, ³Rubén Burgos-Vargas
¹Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Col. Sección XVI, Tlalpan 14080, Mexico City, Mexico, ²Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14000, Mexico City, Mexico, ³Department of Rheumatology, Hospital General de Mexico, Dr. Balmis 146, Col. Doctores, Cuauhtemoc 06726, Mexico City, Mexico

The spondyloarthropathies (SpA) are a heterogeneous group of diseases characterized by axial as well as peripheral enthesitis and arthritis and less frequently by a range of extra-articular manifestations. The strong association between HLA-B27 and the SpA, particularly ankylosing spondylitis (AS) in the general population and in first degree relatives of affected individuals confers this allele a significant role in disease susceptibility. Yet, the fact that only approximately 2% of HLA-B27 individuals develop AS and that a small proportion of patients with AS does not carry the B27 allele suggests other genes within the major histocompatibility complex (MHC) participate in the disease susceptibility process. Thus, other new genes detected in this region have been studied. Of special interest is the TNF-alpha gene that codified a potent proinflammatory cytokine and immune modulator which in certain conditions is involved in joint destruction. The aim of the present study was to investigate the allele distribution of TNF-alpha polymorphism in a group of SpA Mexican patients. One hundred and fifty-two patients with SpA (77 with undifferentiated SpA, 52 with ankylosing spondylitis (AS), and 23 with reactive arthritis (ReA)) and 99 healthy controls were studied. The HLA-B alleles were detected by PCR-SSP technique and the TNF-alpha polymorphism (positions -238 and -308) were determined by PCR-RFLP. Statistical methods included the Mantel-Haenzel, X2, Fisher's exact test, and Woolf method for odds ratio (OR). TNF-238 polymorphism analysis showed significant increased frequency of - 238 A/G genotype in AS patients when compared to healthy controls (pC<0.05, OR=2.7). This difference not remain significantly increased when we analyzed only the B27 negative patients. On the other hand, TNF-308.A allele was increased in the whole group of SpA (pC<0.05, OR=3.8) patients, whereas, undifferentiated SpA patients presented an increased frequency of -308 G/A genotype when compared to healthy controls (pC<0.05, OR=3.5). These differences remained significantly increased when we analysed only the B27 negative patients. Thus, significant increased frequency of TNF-308.A allele was detected in B27 negative SpA patients (pC<0.05, OR=4.2). HLA-B27 negative patients with undifferentiated SpA showed significant increased frequencies of TNF-308A allele and -308G/A genotype when compared to B27 negative healthy controls (pC<0.05, OR=5.0 and pC<0.05, OR=3.5, respectively). In conclusion, the present study demonstrates that the SpA in the Mexican Mestizo patients, besides associating with the HLA-B27, associates with some TNF-alpha alleles. This association seems independent of the susceptibility conferred by the HLA-B27 in the undifferentiated SpA group of patients.