Daniel Čierny1, Ján Lehotský2, Ema Kantorová3, Štefan Sivák3, Juraj Javor4, Egon Kurča3, Dušan Dobrota1,2, Jozef Michalik3. 1. a Jessenius Faculty of Medicine, Department of Clinical Biochemistry , Comenius University in Bratislava and University Hospital Martin , Martin , Slovak Republic. 2. b Jessenius Faculty of Medicine in Martin, Department of Medical Biochemistry and BioMed , Comenius University in Bratislava , Martin , Slovak Republic. 3. c Jessenius Faculty of Medicine, Clinic of Neurology , Comenius University in Bratislava and University Hospital Martin , Martin , Slovak Republic. 4. d Faculty of Medicine, Institute of Immunology , Comenius University in Bratislava , Bratislava , Slovak Republic.
Abstract
OBJECTIVE: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population. METHODS: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5th, 7th, 10th, and 15th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers. RESULTS: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5th year of disease duration was found in carriers of DRB1*07 allele (p cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p cor = 0.0305). DISCUSSION: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.
OBJECTIVE: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population. METHODS: The allele and genotype variants were analyzed in 282 non-related MSpatients. Rate of disease disability progression was evaluated using EDSS score in the 5th, 7th, 10th, and 15th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers. RESULTS: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5th year of disease duration was found in carriers of DRB1*07 allele (p cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MSpatients, when compared to MSpatients with mid-rate and rapid disease disability progression (p cor = 0.0305). DISCUSSION: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MSpatients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.