HLA-DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population.
OBJECTIVE
The association of HLA-DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA-DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population.


METHODS
HLA-DRB1 typing was performed by PCR-SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS.


RESULTS
The HLA-DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR)=2.07, 95% CI=1.64-2.60, P<0.001). In the univariate analysis, the DRB1*01 and DRB1*04 alleles were associated with a worse prognosis when considering the time to reach an EDSS of 6, whereas the DRB1*03 was correlated with a better outcome. In the multivariate analysis, the alleles*01 and *04 were demonstrated to be independent factors to have a worse prognosis.


CONCLUSIONS
HLA-DRB1*15 is associated with MS when comparing patients with unrelated healthy controls in a Spanish population. The HLA-DRB1*01 and HLA-DRB1*04 alleles are related to a worse prognosis when considering the time taken to reach severe disability.
Romero-Pinel
L
L
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
Pujal
J M
JM
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
Martínez-Yélamos
S
S
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
Gubieras
L
L
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
Matas
E
E
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
Bau
L
L
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
Torrabadella
M
M
Banc de cordó umbilical, Banc de sang i teixits, Barcelona, Spain.
Azqueta
C
C
Banc de cordó umbilical, Banc de sang i teixits, Barcelona, Spain.
Arbizu
T
T
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.
D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013030:Spain / Q000453:epidemiology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains