Allelic variations of DPB1, DQA1, DQB1 and DRB1 and rheumatoid arthritis: further genetic and statistical considerations [Varianti alleliche dei DPB1, DQA1, DQB1, DRB1 e artite reumatoide: ulteriori considerazioni genetiche e statistiche]

We used polymerase chain reaction amplification and hybridization with specific oligonucleotides to analyze the distribution of DPB1, DQA1, DQB1, and DRB1 allelic variants in 48 patients with rheumatoid arthritis (RA) and compared our results with those from 109 randomly chosen, healthy control subjects. Our work confirms a previously reported increase in DR4 specificity in RA: in particular, we found a statistically significant positive association of the DRB1*0401 and DRB1*0404 alleles with RA. When we compared the DR4 groups, however, none of the DRB1*04 alleles were increased in the RA group. Molecular analysis of the other DRB1 polymorphic variants disclosed the trend of a positive association of DRB1*0101 (DR1) in DR4 negative patients vs DR4 negative healthy control subjects, and an increase in DRw6 (DRB1*13,*14) in the DR4 and/or DR1 negative patient group. Moreover, analysis of the association between RA and a heptapeptide motif (positions 67-74) in the third hypervariable region confirmed that this epitope confers enhanced risk for the development of RA with respect to the allele DRB1*0404 (etiologic fraction = 0.53 vs 0.12). We also observed a statistically significant increase in DQA1*0301 and DQB1*0302 accompanied by a significant decrease in DQA1*0202, DQA1*0501 and DQB1*0201 in RA patients. Analysis of DPB1 alleles disclosed no significant differences between RA patients and healthy control subjects.