CC chemokine receptor 5 polymorphism in rheumatoid arthritis.
OBJECTIVE
Some chemokine receptors have been shown to be co-receptors for human immunodeficiency virus (HIV-1). A 32 base pair deletion allele in the CC chemokine receptor 5 gene (CCR5 delta32 allele) affects both transmission of HIV-1 and acquired immunodeficiency syndrome (AIDS)-free survival. Chemokines are suggested to be critical for establishment of inflammatory processes in autoimmune diseases such as rheumatoid arthritis (RA). We hypothesized that the defective allele may modulate the inflammatory process in RA.


METHODS
Using polymerase chain reaction methods, we investigated the significance of the CCR5 delta32 allele in 163 Danish patients with RA and monitored clinical and paraclinical variables.


RESULTS
The gene frequency of the CCR5 delta32 allele (0.10) did not deviate significantly from healthy controls and from that reported in healthy Caucasian populations, nor did the distribution deviate from the Hardy-Weinberg predictions (131 wild type, 30 heterozygous, 2 homozygous for the deletion allele; p = 0.85). However, a significantly increased proportion of those carrying the deletion allele were negative for IgM rheumatoid factor (RF) compared to those homozygous for the normal allele (29 vs 9%; p = 0.007). The proportion of CCR5 delta32 allele carriers with swollen joints was decreased compared to those homozygous for the normal allele (35 vs 58%, respectively; p = 0.03), as was the duration of morning stiffness (median 0 vs 60 min, respectively; p = 0.0002).


CONCLUSIONS
The CCR5 delta32 allele seems to have some influence on RA variables including RF, which suggests that inhibition of chemokine receptors might be a potential target for disease modifying therapy in RA.
Department of Clinical Immunology, The National University Hospital (Rigshospitalet), Copenhagen, Denmark. Garred@post5.tele.dk
P
P
Garred
H O
HO
Madsen
J
J
Petersen
H
H
Marquart
T M
TM
Hansen
S
S
Freiesleben Sørensen
B
B
Volck
A
A
Svejgaard
V
V
Andersen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics*; D001327:Autoimmune Diseases; D015551:Autoimmunity; D065100:CCR5 Receptor Antagonists; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D011991:Receptors, Virus / Q000235:genetics; D012217:Rheumatoid Factor / Q000378:metabolism
D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5; D011991:Receptors, Virus; D012217:Rheumatoid Factor