HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations

Maria C Anagnostouli,Argyro Manouseli

doi:10.4172/jmso.1000104

Abstract

Studies in many populations consistently have showed that the human leukocyte antigens (HLA) and especially the DRB1*15 allele has by far the strongest genetic association with multiple sclerosis (MS). The aim of this study was to investigate the role of HLA-DRB1* alleles in MS risk/resistance and onset. A sample of 165 Hellenic MS patients (18 with pediatric-, 24 with adolescent- and 123 with adult-onset MS) and 107 healthy volunteers were examined with molecular techniques. Comparisons were made according to the Benjamini-Yekutieli method for p value correction. Both adult-onset MS patients and early-onset MS patients (age at onset below 20 years-old) had a significantly higher frequency of the DRB1*15 allele and a significantly lower frequency of the DRB1*11 allele compared to controls. For the early-onset vs. healthy group comparison, subgroup analyses revealed that both the pediatric- and the adolescent-onset MS groups contributed to the aforementioned DRB1*15 significant difference, while the DRB1*11 difference was ascribed solely to the adolescent-MS onset vs. healthy group comparison. Within MS patients comparisons revealed that early-onset MS patients had a tendency for higher DRB1*03 allele and a lower DRB1*16 allele frequency frequencies compared to adult-onset MS patients, although both non-significant. Notably, pediatric-onset MS patients showed complete absence of the DRB1*16 allele, along with a non-significant tendency for higher DRB1*15 allele frequency relative to the adult-onset group. Finally, the adolescent-onset MS group was presented with a lower DRB1*11 allele frequencies compared both to the pediatric- and the adult-onset MS group. Our findings confirm previous studies on the role of HLA-DRB1* in MS. New findings that need to be confirmed by further studies are the pathogenetic role of DRB1*03 for early-onset MS and the putative protective role of the DRB1*16 allele in the pediatric-onset MS.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) of unknown origin
The adolescent group showed non-significant difference with the adult group, a tendency for higher DRB1*03 allele frequency and lower DRB1*11 allele frequency was noted (Table 8). This is the first study aiming at revealing the human leukocyte antigens (HLA)-DRB1* allelic distribution in early-onset and adult-onset MS, in the Hellenic population
Our findings are in part new and in part standard, concerning previous results of HLA frequencies in Hellenic MS patients and HLAgenotyping in various other populations

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) of unknown origin. Both environmental and genetic factors have been implicated in the pathogenesis of the disease leading to the well-known consideration of MS as a complex multi-factorial disease entity [1]. Concerning genetics, linkage studies in many populations consistently have showed that the human leukocyte antigens (HLA), products of the. Major Histocompatibility Complex (MHC) on chromosome 6p21.3 are linked to MS [1,2]. MHC represents a cluster of highly polymorphic genes, including the HLA-Class I, II and III genes that encode proteins which serve antigen presentation to T-lymphocytes.

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