Association of CCR5 delta32 deletion with early death in multiple sclerosis.
OBJECTIVE
The interaction between chemokines and their receptors is extremely important in controlling T cell migration into sites of CNS inflammation. Because trafficking of inflammatory T cells into the central nervous system (CNS) is a key player in the pathogenesis of multiple sclerosis (MS), we investigated the possible association of CCR5 delta32 deletion in this disorder.


METHODS
DNA isolated from postmortem brain tissue samples of 132 patients with MS and from blood tissue samples of 163 gender and ethnicity-matched healthy controls was used to screen for the CCR5 delta32 deletion allele.


RESULTS
An increased frequency of 32-bp deletion allele was found to be associated with early death (P = 0.00005) and with a progressive reduction in the years of survival (onset to death). The death hazard ratio of CCR5 with deletion versus no deletion was 2.12, suggesting that MS patients with the 32-bp deletion have twice the mortality rate of patients with the normal genotype. This effect was more significant in females (hazard ratio 3.58).


CONCLUSIONS
A strong association of the CCR5delta32 deletion with early death could serve as a prognostic marker for MS.
Gade-Andavolu
Radhika
R
Genetic Research Institute of the Desert, Eisenhower Medical Center, Rancho Mirage, California 92270, USA.
Comings
David E
DE
MacMurray
James
J
Rostamkhani
Masoud
M
Cheng
Li S-C
LS
Tourtellotte
Wallace W
WW
Cone
Lawrence A
LA
D000483:Alleles; D016022:Case-Control Studies; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D019713:Receptors, CCR5