The role of HLA-DRB1 alleles on susceptibility and outcome of a Portuguese Multiple Sclerosis population.
Silva AM., Pereira C., Bettencourt A., Carvalho C., Couto AR., Leite MI., Marta M., Freijo M., Costa PP., Mendonça D., Monteiro L., Armas JB., Martins B.
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.