title: HLA-DRB1* allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients.
abstract: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system that causes neurological disorders in young adults. Previous studies in various populations highlighted an association between the HLA-DRB1*15 allele and MS. This study investigated the association between HLA-DRB1*15 and other HLA-DRB1 alleles and MS in a Brazilian Caucasian population sample from Londrina, Southern Brazil. HLA-DRB1 alleles were analyzed by polymerase chain reaction with specific sequence oligonucleotide primers in 119 MS patients and in 305 healthy blood donors as a control. Among the MS patients, 89 (75.0%) presented with relapsing remitting MS, 24 (20.0%) with secondary progressive MS and 6 (5.0%) with primary progressive MS. The frequency of the HLA-DRB1*15 allele observed in the MS Brazilian patients was similar to findings reported in previous studies carried out in populations worldwide. However, the results showed a higher frequency of the HLA-DRB1*15 allele in the MS patients compared to the controls, with a relative frequency of 0.1050 (10.50%) and 0.0443 (4.4%), respectively (OR=2.53; 95% CI 1.43-4.46; p=0.0009). A protector allele was also detected. The frequency of the HLA-DRB1*11 allele was reduced in the MS patients compared to the controls, with a relative frequency of 0.1345 (13.4%) and 0.1869 (18.7%), respectively (OR=0.67; 95% CI 0.44-1.03; p=0.0692). The results demonstrated that the HLA-DRB1*15 allele in heterozygosity is positively associated with MS (p=0.0079), and may be considered a genetic marker of susceptibility to the disease. A negative association between the HLA-DRB1*11 allele in homozygosity and MS was also verified (p=0.0418); this allele may be considered a genetic marker of resistance to MS in the Brazilian population.
authors.affiliation: Department of Clinical Medicine, Health Sciences Center, University Hospital, State University of Londrina, Paraná, Brazil.
authors.forename: Damacio R
authors.initials: DR
authors.lastname: Kaimen-Maciel
authors.forename: Edna Maria V
authors.initials: EM
authors.lastname: Reiche
authors.forename: Sueli D
authors.initials: SD
authors.lastname: Borelli
authors.forename: Helena K
authors.initials: HK
authors.lastname: Morimoto
authors.forename: Fabiano C
authors.initials: FC
authors.lastname: Melo
authors.forename: Josiane
authors.initials: J
authors.lastname: Lopes
authors.forename: Raffael F
authors.initials: RF
authors.lastname: Dorigon
authors.forename: Christiane
authors.initials: C
authors.lastname: Cavalet
authors.forename: Elton M
authors.initials: EM
authors.lastname: Yamaguchi
authors.forename: Thiago L
authors.initials: TL
authors.lastname: Silveira
authors.forename: Waldir V
authors.initials: WV
authors.lastname: Da Silva
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Comini-Frota
authors.forename: Doralina G
authors.initials: DG
authors.lastname: Brum Souza
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi