A DNA polymorphism at the alpha(2)-macroglobulin gene is associated with the severity of rheumatoid arthritis

Objective. To determine if DNA polymorphisms at the alpha(2)-macroglobulin (alpha(2)m) and angiotensin converting enzyme (ACE) genes were associated w ith rheumatoid arthritis (RA). Methods. A total of 160 patients (71 with early active severe RA, 89 with n on-severe RA) were genotyped (polymerase chain reaction) for the alpha(2)m (5 bp deletion/insertion) and ACE (I/D) polymorphisms. We also genotyped 50 0 healthy controls from the same Caucasian population (Asturias, Northern S pain). Results. Carriers of the alpha(2)m deletion allele were at a significantly higher frequency among patients with an early active severe form of the dis ease, compared to patients with non-severe RA (p = 0.037). The frequency of the alpha(2)m deletion allele was significantly higher in patients with se vere compared to nonsevere RA (p = 0.017). In addition, the frequency of th e deletion allele was significantly higher among patients with 5 or more ep isodes of acute exacerbation of disease activity per year (n = 39) compared to those with none (n = 46) (p = 0.002). Gene and genotype frequencies for the ACE-I/D polymorphism did not differ between those with early active se vere and non-severe RA. Conclusion. The genetic variation at alpha(2)m is associated with the sever ity of RA. Carriers of the alpha(2)m deletion allele would have increased r isk of developing an early active severe form of the disease. Our data sugg est that alpha(2)m could he a valuable target in the treatment of RA.