Chemokine receptor 5 (CCR5) delta 32 polymorphism in lupus nephritis: a large case-control study and meta-analysis.
OBJECTIVE
Recent animal experiments showed that CCR5-deficient lupus mice (CCR5(-/-)) were closely associated with aggravated lupus nephritis. CCR5 Δ32 variation, a nonsynonymous mutation of CCR5, resulted in altered CCR5 function. However, the CCR5 Δ32 mutation in human lupus nephritis has been rarely reported in the literature.


METHODS
A large case-control study that included 2010 samples from a Chinese population was conducted, followed by a meta-analysis combining the current and previously published studies to explore the effect of CCR5 Δ32 on lupus nephritis susceptibility.


RESULTS
Four CCR5 Δ32 heterozygote carriers were detected in lupus nephritis patients only. We detected no CCR5 Δ32 homozygotes in our study population. In the meta-analysis, including 1,092 cases and 2,229 controls, we found great heterogeneity between studies (p < 0.001, I(2)( )= 89.6%). Furthermore, stratified and sensitivity analyses suggested that ethnicity and CCR5 Δ32 allele frequency were the main origin of heterogeneity. In the subgroups without obvious heterogeneity, we observed a positive correlation between CCR5 Δ32 and lupus nephritis risk (p < 0.05).


CONCLUSIONS
Our study confirmed that the CCR5 Δ32 mutation is a very rare variation found in the Chinese population with Han ethnicity. However, CCR5 Δ32 might play a role in lupus nephritis susceptibility. Future replications and functional studies are needed.
Renal Division, Department of Medicine, Peking University First Hospital , Beijing , China .
Fa-Juan
FJ
Cheng
Xu-Jie
XJ
Zhou
Yan-Feng
YF
Zhao
Ming-Hui
MH
Zhao
Hong
H
Zhang
D016022:Case-Control Studies; D002681:China; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics*; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*
C584933:CCR5 protein, human; D019713:Receptors, CCR5
Chinese Han ethnicity; complex autoimmune disease; functional genetic variant; susceptibility; systemic lupus erythematosus