title: The role of HLA-DRB1 alleles on susceptibility and outcome of a Portuguese Multiple Sclerosis population.
abstract: BACKGROUND
  The association between susceptibility to multiple sclerosis (MS) and HLA-DRB1*15 has been reported in various European populations.
  
  
  OBJECTIVE
  To investigate the relationship between MS, HLA-DRB1*15 and other DRB1 alleles in a Portuguese population and their association with clinical course of MS.
  
  
  METHODS
  The HLA-DRB1 alleles were analyzed by PCR-SSP in 248 MS patients and 282 healthy controls. In order to relate HLA-DRB1 alleles to disease aggressiveness, patients with relapsing remitting MS and secondary progressive MS were subdivided into 3 groups: 'benign' MS patients who maintain an Extended Disability Status Scale (EDSS) score of <or=3 at least 10 years after disease onset; non-benign MS patients with EDSS>3 after the same period and 'aggressive' MS those with EDSS>or=6 within 15 years of disease onset.
  
  
  RESULTS
  As expected, a higher frequency of HLA-DRB1*15 was found in MS patients (29.8% vs 19.9%, odds ratio (OR)=1.72, 95% CI=1.15-2.56, p=0.008). The HLA-DRB1*03 allele was positively associated with MS in the overall patient population (22.6% vs 15.6%, OR=1.58, 95% CI=1.02-2.45). Concerning disease aggressiveness, HLA-DRB1*15 occurred more frequently in the group with benign disease (42.6% vs 19.9%, OR=2.99, 95% CI=1.56-5.72) and in the group with non-benign disease (34.1% vs 19.9%, OR=2.09, 95% CI=1.05-4.16) compared with controls. When time to reach an EDSS=3 or EDSS=6 was considered as end point, HLA-DRB1*15 negative patients were found to have a worse prognosis.
  
  
  CONCLUSIONS
  In this population of Portuguese MS patients, the HLA-DRB1*15 allele is established as a genetic marker for susceptibility to MS and is also associated with a better outcome.
authors.affiliation: Department of Neurology, Hospital Santo António, Porto, 4005-001 Porto, Portugal. anadmsilva@yahoo.com
authors.forename: Ana Martins
authors.initials: AM
authors.lastname: Silva
authors.forename: Clara
authors.initials: C
authors.lastname: Pereira
authors.forename: Andreia
authors.initials: A
authors.lastname: Bettencourt
authors.forename: Cláudia
authors.initials: C
authors.lastname: Carvalho
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Couto
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Leite
authors.forename: Mónica
authors.initials: M
authors.lastname: Marta
authors.forename: Marta
authors.initials: M
authors.lastname: Freijo
authors.forename: Paulo Pinho
authors.initials: PP
authors.lastname: Costa
authors.forename: Denisa
authors.initials: D
authors.lastname: Mendonça
authors.forename: Luís
authors.initials: L
authors.lastname: Monteiro
authors.forename: Jácome Bruges
authors.initials: JB
authors.lastname: Armas
authors.forename: Berta
authors.initials: B
authors.lastname: Martins
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D004185:Disability Evaluation; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D011174:Portugal / Q000453:epidemiology; D011336:Probability; D016019:Survival Analysis
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains