HLA class II polymorphism in Latin American patients with multiple sclerosis.
OBJECTIVE
To identify HLA-DRB1 alleles contributing to susceptibility to multiple sclerosis (MS) in a Colombian population and to estimate the common effect size of HLA class II on MS susceptibility in Latin American populations through a meta-analysis.


METHODS
A total of 65 Colombian patients with MS and 184 matched controls were included. HLA-DRB1 typing was done using the sequence-specific oligonucleotide probe method. A bivariate and a multivariate logistic regression analyses were done. Case-control studies performed in Latin America were searched up to January 2009 through a systematic review of the literature. Effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model.


RESULTS
A total of 464 cases and 2581 controls from 7 studies and the results of the present study in Colombians were analyzed. HLA-DRB1*15 (OR: 2.3; 95% CI: 1.68-3.07; p<0.001) and HLA-DQB1*06 (OR: 2.2; 95% CI: 1.54-3.07; p<0.001) groups as well as DRB1*1501 (OR: 2.6; 95% CI: 1.67-4.02; p<0.001), DRB1*1503 (OR: 2.2; 95% CI: 1.39-3.62; p=0.001) and DQB1*0602 (OR: 2.5; 95% CI: 1.66-3.71; p<0.001) alleles were found to be risk factors for MS. The myelin basic protein immunodominant sequence (221)VHFFKNIVT(229) was predicted to strongly and simultaneously bind to HLA-DRB1*1501 and *1503.


CONCLUSIONS
The current study highlights the effect size of HLA class II in MS in Latin America and confirms similar allelic risk factors across diverse populations. Receptor-ligand interactions in the HLA-antigenic peptide complex could have potential predictive and therapeutical implications.
Rojas
Olga-Lucía
OL
Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
Rojas-Villarraga
Adriana
A
Cruz-Tapias
Paola
P
Sánchez
Jorge Luis
JL
Suárez-Escudero
Juan-Camilo
JC
Patarroyo
Manuel-Alfonso
MA
Anaya
Juan-Manuel
JM
D001324:Autoantigens / Q000378:metabolism; D016022:Case-Control Studies; D003105:Colombia; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011110:Polymorphism, Genetic; D011485:Protein Binding; D012307:Risk Factors
D001324:Autoantigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D004676:Myelin Basic Protein; D010446:Peptide Fragments