The role of HLA-DRB1 alleles on susceptibility and outcome of a Portuguese Multiple Sclerosis population Ana Martins Silva a, ⁎ , Clara Pereira b , Andreia Bettencourt b , Cláudia Carvalho b,c , Ana Rita Couto e , Maria Isabel Leite a,1 , Mónica Marta a,2 , Marta Freijo a,3 , Paulo Pinho Costa b,c , Denisa Mendonça d , Luís Monteiro a , Jácome Bruges Armas e , Berta Martins b,c a Department of Neurology, Hospital Santo António, Porto, 4005-001 Porto, Portugal b Immunogenetics Laboratory-ICBAS/University of Porto, Portugal c Immunogenetics Laboratory-INSA-Dr. Ricardo Jorge, Porto, Portugal d Department of Population Studies, Biometry Laboratory, ICBAS/IBMC Porto, Portugal e SEEBMO, Hospital de Santo Espírito de Angra do Heroísmo, Azores, Portugal Received 25 July 2006; received in revised form 29 January 2007; accepted 21 February 2007 Available online 6 April 2007 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 ≤ 3 at least 10 years after disease onset; non-benign MS patients with EDSS N 3 after the same period and ‘aggressive’ MS those with EDSS ≥ 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. © 2007 Elsevier B.V. All rights reserved. Keywords: Multiple sclerosis; HLA; Portugal; DRB1 ⁎ 15; Class II 1. Introduction Multiple Sclerosis (MS) is the most common inflamma- tory demyelinating disease of the central nervous system (CNS) in young adults. The cause of MS is unknown, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals after exposure to as-yet undefined environmental factors [1]. Although the nature of Journal of the Neurological Sciences 258 (2007) 69 – 74 www.elsevier.com/locate/jns ⁎ Corresponding author. Tel.: +351 22 2077500; fax: +351 22 2062232. E-mail address: anadmsilva@yahoo.com (A.M. Silva). 1 Present address: Neurosciences Group, Department of Clinical Neurol- ogy, University of Oxford, OX3 9DU, UK. 2 Present address: Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Institute, 17176, Stockholm, Sweden. 3 Present address: Serviço de Neurologia, Hospital Distrital de Mirandela, Portugal. 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.02.033