Study of Association Between the Polymorphism of MICA Gene (met 129 val) and Ankylosing Spondylitis in a Sample of the Population of Western Algeria

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatism characterized by a predominantly axial (spinal) localization, followed by joint damage and enthesis. The AS may be associated with other conditions such as reactive arthritis, psoriatic arthritis, chronic inflammation of the intestine and pulmonary manifestation. In this case, we speak of Spondylarthroparies (SPA). The etiology of AS is not well known, however, genetic factors as well as environmental factors can play a very important role in the onset of the disease. Although several genes appear to be associated with SA, the concept of genetic ground relies heavily on the association with HLA-B27 specificity. Recently, the MICA gene has aroused the interest of several studies of associations MICA and autoimmune diseases (MAI), in particular, the association MICA and SA. In our work, we are interested in the polymorphism existing at exon 3 and which encodes the α2 domain of the MICA protein. This polymorphism has the position 129 either the methionine (met) allele or the valine (val) allele. MICA proteins with methionine residue at position 129 react strongly with its NKG2D receptors found on the surface of NK and LT, thereby increasing the cytotoxicity threshold. In contrast, MICA proteins that have a valine residue at the same position have a low affinity with NKG2D. This weakens the threshold of cytotoxicity. The aim of our work is to look for the associations between the polymorphism MICA met129val and the SA in a sample of 90 cases suffering from the SA and 78 controls, within the population of western Algeria. We then tested the effect of this polymorphism on HLA-B27 status. Finally, we looked for a possible association between the MICA-129 genotyping and the early onset of SA. The results show that the MICA-129met allele is strongly associated with SA in patients compared to controls since it is found at an allelic frequency of 0.54 vs 0.30 (p=11.10-6). On the other hand, the MICA-129val allele is strongly found in the controls than in the cases, with a frequency of 0.70 vs 0.46 (p=11.10-4). However, the polymorphism MICA met129val showed no synergistic or independent effect on the distribution of HLA-B27 specificity in either cases or patients. It is interesting in this case to study other interactions between this polymorphism and other genes or alleles already associated with SA. In our work, we could not determine the effect of MICA-129 genotypes on the early onset of the disease, as reported by another similar study carried out in an Algerian population.