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Influence of C C R5 32 polymorphism on multiple sclerosis susceptibility and disease course

Department of Medical Genetics, Queens University of Belfast, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland

S V Heggarty

Northern Ireland Regional Genetics Centre, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland

G V McDonnell

Northern Ireland Regional Neurology Service, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, Northern Ireland

S A Hawkins

Department of Medicine, Queens University of Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BA, Northern Ireland

C A Graham

Northern Ireland Regional Genetics Centre, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, colin.graham{at}bll.n-i.nhs.uk

The C C R5 chemokine receptor has been implicated in the patho genesis of multiple sclerosis (MS). We carried out an allelic association study using a deletion polymorphism in the coding region of the C C R5 gene in 331 relapsing-remitting (RR) and secondary progressive (SP) MS patients, 108 primary progressive (PP) MS patients and 230 healthy controls. O f 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 C C R5 d32 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 d32 allele. In the population-based group of RR/SPMS patients, carriage of the C C R5 d32 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 C C R5 d32 polymorphism is not a major determinant of susceptibility to develop MS in the population under study, and conflict with a previously reported association between C C R5 d32 carriage and a better prognosis.

Key Words: autoimmunity • C C R5 • chemokine receptors • chemokines • human • multiple sclerosis • receptors

Multiple Sclerosis, Vol. 10, No. 2, 149-152 (2004)
DOI: 10.1191/1352458504ms994oa


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