title: The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis.
abstract: BACKGROUND
  Genetic and pharmacological inactivation of cannabinoid CB(1) receptors (CB(1)Rs) exacerbates disease course in experimental autoimmune encephalomyelitis, suggesting that CB(1)Rs might play a role in the neurodegenerative damage associated with multiple sclerosis (MS).
  
  
  OBJECTIVE
  To see whether CNR1 gene polymorphism could influence disease progression in relapsing-remitting MS.
  
  
  METHODS
  The genotype of 350 patients for the number of AAT repeats was characterized and correlation studies were performed with measures of disease severity and progression.
  
  
  RESULTS
  MS patients with the homozygous genotype for long AAT repeats in the CNR1 gene had more severe disease and higher risk of progression. These subjects had significantly higher scores on both the progression index and the MS severity scale. Furthermore, the percentage of patients with MS functional composite score progression or Bayesian Risk Estimate for MS (BREMS) score ≥ 2 (considered at very high risk of secondary progression) was significantly higher in the AAT long group than in the short group, while the frequency of patients with BREMS score ≤-0.63 (very likely to remain progression-free) was not significantly different between the two groups, although lower in the long group. Finally, the frequency of patients prescribed a second-line treatment was significantly higher among subjects of the AAT long group, providing a further, indirect indication of higher disease severity.
  
  
  CONCLUSIONS
  The results of the present investigation point to CB(1)R as an important modulator of disease severity in relapsing MS subjects.
authors.affiliation: Dipartimento di Neuroscienze, Università Tor Vergata, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Fabio
authors.initials: F
authors.lastname: Buttari
authors.forename: Valeria
authors.initials: V
authors.lastname: Studer
authors.forename: Caterina
authors.initials: C
authors.lastname: Motta
authors.forename: Paolo
authors.initials: P
authors.lastname: Gravina
authors.forename: Maura
authors.initials: M
authors.lastname: Castelli
authors.forename: Vilma
authors.initials: V
authors.lastname: Mantovani
authors.forename: Valentina
authors.initials: V
authors.lastname: De Chiara
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.forename: Stefania
authors.initials: S
authors.lastname: Fiore
authors.forename: Silvia
authors.initials: S
authors.lastname: Masini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007558:Italy; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D018911:Trinucleotide Repeats; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D043884:Receptor, Cannabinoid, CB1