Influence of CCR5 delta32 polymorphism on multiple sclerosis susceptibility and disease course.
The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). We carried out an allelic association study using a deletion polymorphism in the coding region of the CCR5 gene in 331 relapsing-remitting (RR) and secondary progressive (SP) MS patients, 108 primary progressive (PP) MS patients and 230 healthy controls. Of the 331 RR and SPMS patients, 172 were recruited from specialist clinics and 159 from a population survey. Disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS) and used to calculate a progression index for each patient (defined as EDSS divided by duration of disease). No significant difference in distribution of the CCR5 delta32 allele was observed between the 331 RR/SPMS patients and controls, between the 108 PPMS patients and controls or between the PPMS and RR/SPMS groups. Furthermore, no differences in rate of disease progression were detected between carriers and noncarriers of the delta32 allele. In the population-based group of RR/SPMS patients, carriage of the CCR5 delta32 polymorphism was associated with a lower age at disease onset (mean age 26.562 versus 31.065 years, P = 0.003). However, no significant differences in age of onset were present in the PPMS group or in a second RRMS population. These results suggest that the CCR5 delta32 polymorphism is not a major determinant of susceptibility to develop MS in the population under study, and conflict with a previously reported association between CCR5 delta32 carriage and a better prognosis.
Silversides
J A
JA
Department of Medical Genetics, Queens University of Belfast, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland.
Heggarty
S V
SV
McDonnell
G V
GV
Hawkins
S A
SA
Graham
C A
CA
D000328:Adult; D017668:Age of Onset; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D020528:Multiple Sclerosis, Chronic Progressive / Q000453:epidemiology / Q000235:genetics*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology / Q000235:genetics*; D009660:Northern Ireland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D015995:Prevalence; D019713:Receptors, CCR5 / Q000235:genetics*
D019713:Receptors, CCR5