Polymorphisms of the cannabinoid 1 receptor gene and cognitive impairment in multiple sclerosis

¹ Human Genomics Research Group, Institute of Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, University Hospital of North Staffordshire, Stoke on Trent, Staffordshire ST4 7LN, UK
² School of Psychology, Keele Universtity, Keele, Staffordshire ST5 5BG, UK
³ School of Computing and Mathematics, Keele University, Keele, Staffordshire ST5 5BG, UK
⁴ Department of Psychology, Royal Holloway, University of London, London TW20 0EX, UK

^* To whom correspondence should be addressed.

	Abstract

Cognitive impairment occurs in 45–65% of multiple sclerosis (MS) patients. The cannabinoid system may potentially be neuroprotective in MS. We examined the relationship between polymorphisms of the CNR1 gene and neuropsychological outcome in MS using a test and confirmatory sample of patients. One hundred and ninety-four MS patients were assessed over five key areas of neuropsychological function, which are most commonly impaired in MS. The first 97 patients formed the test sample. A further confirmatory sample of 97 patients was used to test association found in the test sample. The schedule included: Wisconsin card sorting test 64 version, Rey auditory verbal learning task immediate and delayed scores, controlled oral word association task, judgement of line orientation and symbol digit modalities task. Three single nucleotide polymorphisms (SNPs) were typed within the CNR1 gene.

For the overall neuropsychological assessment score we used a multiple linear regression model with selected covariates to show that subjects with the AA genotype of the SNP RS1049353 were more impaired (mean 22.47, SD 5.75, P 5 0.008, Bonferroni corrected P 5 0.024) than the other subjects (mean 0.24, SD 4.24). This was not confirmed when the association was retested in the confirmatory sample.

No associations were identified between these CNR1 variants and cognitive impairment in MS. Multiple Sclerosis 2007; 00: 00–00. http://msj.sagepub.com

Key Words: cannabinoid receptor; disease progression; genetic; multiple sclerosis; neuropsychology; polymorphisms

First published on October 17, 2007, doi:10.1177/1352458507081343

Multiple Sclerosis 2008;14:177.

A more recent version of this article appeared on March 1, 2008


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