A DNA polymorphism at the alpha2-macroglobulin gene is associated with the severity of rheumatoid arthritis.
OBJECTIVE
To determine if DNA polymorphisms at the alpha2-macroglobulin (alpha2m) and angiotensin converting enzyme (ACE) genes were associated with rheumatoid arthritis (RA).


METHODS
A total of 160 patients (71 with early active severe RA, 89 with non-severe RA) were genotyped (polymerase chain reaction) for the alpha2m (5 bp deletion/insertion) and ACE (I/D) polymorphisms. We also genotyped 500 healthy controls from the same Caucasian population (Asturias, Northern Spain).


RESULTS
Carriers of the alpha2m deletion allele were at a significantly higher frequency among patients with an early active severe form of the disease, compared to patients with non-severe RA (p = 0.037). The frequency of the alpha2m deletion allele was significantly higher in patients with severe compared to nonsevere RA (p = 0.017). In addition, the frequency of the deletion allele was significantly higher among patients with 5 or more episodes 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 severe and non-severe RA.


CONCLUSIONS
The genetic variation at alpha2m is associated with the severity of RA. Carriers of the alpha2m deletion allele would have increased risk of developing an early active severe form of the disease. Our data suggest that alpha2m could be a valuable target in the treatment of RA.
Zapico
I
I
Servicio Reumatología and Genética Molecular, Instituto Reina Sofía de Investigacíon Nefrológica, Hospital Central de Asturias, Oviedo, Spain.
Coto
E
E
Rodríguez
A
A
Alvarez
C
C
Torre
J C
JC
Alvarez
V
V
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000145:classification / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D000511:alpha-Macroglobulins / Q000145:classification / Q000235:genetics*
D017931:DNA Primers; D000511:alpha-Macroglobulins; D004247:DNA; D007703:Peptidyl-Dipeptidase A