Lack of association of C-C chemokine receptor 5 Δ32 deletion status with rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, and disease severity.
OBJECTIVE
C-C chemokine receptor 5 (CCR5) plays an important role in inflammation. A 32 base-pair (Δ32) deletion in the CCR5 gene leads to a nonfunctional receptor. This deletion has been reported to have a protective effect on the development and progression of several autoimmune diseases. We investigated whether the Δ32 deletion is associated with disease susceptibility in a population of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and lupus nephritis (LN); and whether it is associated with disease severity.


METHODS
DNA samples from 405 RA patients, 97 SLE patients, 113 LN patients, and 431 healthy controls were genotyped for the CCR5 Δ32 deletion. Differences in genotype frequencies were tested between patients and controls. Association of genotypes with disease severity was analyzed.


RESULTS
Genotype frequencies of each group were in Hardy-Weinberg equilibrium. The genotype frequencies of patients did not differ significantly from controls (CCR5/Δ32, Δ32/Δ32: RA 18.3% and 1.2%, respectively; SLE 17.5% and 2.1%; LN 13.3% and 1.8%; controls 20.0% and 2.8%). However, there was a trend for lower Δ32 deletion allele frequency in LN patients compared to controls (p = 0.08). There was no significant association between the CCR5 status and disease severity in RA, SLE, or LN.


CONCLUSIONS
Although an association with LN cannot be excluded, the CCR5 Δ32 deletion does not seem to be a disease susceptibility genotype for RA, SLE, or LN. No significant effect of the Δ32 deletion on disease severity was demonstrated.
Martens
Henk A
HA
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. h.martens@maartenskliniek.nl
Gross
Sacha
S
van der Steege
Gerrit
G
Brouwer
Elisabeth
E
Berden
Jo H M
JH
de Sevaux
Ruud
R
Derksen
Ronald H W M
RH
Voskuyl
Alexandre E
AE
Berger
Stefan P
SP
Navis
Gerjan J
GJ
Kallenberg
Cees G M
CG
Bijl
Marc
M
D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001483:Base Sequence; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D019713:Receptors, CCR5