Background The Transporter associated with antigen processing (TAP) gene products are involved in the processing of endogenous peptides that bind to human leukocyte antigen (HLA) class I molecules and polymorphism within these genes could alter the immune responses, the phenomenon relevant to the development of autoimmunes diseases.
Objectives In this study, we examined the polymorphism of TAP1 and TAP2 genes in patients with rheumatoid arthritis (RA).
Methods TAP1 and TAP2 typing was performed in 138 white RA patients and 100 healthy controls, all of them originating from Eastern France. TAP1 polymorphic residues at position 333 and 637 and amino acid variants 379, 565, 651 and 665 in TAP2 gene were determined using amplification refractory mutation system (ARMS)- PCR. This method enabled us to determine 4 TAP1 alleles (TAP1A to TAP1D) and 8 TAP2 alleles (TAP2A to TAP2H). All patients and controls had been HLA DRB1* genotyped.
Results The polymorphic residues TAP1/333 and TAP1/637 did not show any difference in their distribution between patients and controls.
Similar findings were observed for TAP2/379 and TAP2/665. However, we found an increased frequency of Thr homozygosity and heterozygosity at position 565 in TAP2 gene (RA vs Controls: 25.3% vs 14%; p: 0.032;OR: 2.09;CI: 1.01–4.38). Similarly, the prevalence of subjects who were homozygote and heterozygote for Cys/651 was increased in the RA group (RA vs Controls: 22.4% vs 11%; p:0.02). The frequency of TAP2F was higher in RA patients (24.5%) as compared with controls (11.3%), without significance after correction (p:0.029; p corr: 0.17).
Finally, we found no linkage disequilibrium between DRB1* associated -alleles and amino acid substitution Thr/665 whereas Cys/651 was not independent of DRB1*04, a strongly RA-linked allele.
Only a few patients expressing Thr at position 565 in TAP2 gene were associated with severe clinical manifestations.
Conclusion We evidenced in this study an association between a particular amino acid residue, namely Thr/665 in TAP2 gene, and RA.
This association was found to be weak and did not seem to be a predictor for the severity of the disease.
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