From:  HLA polymorphisms with high expression in multiple sclerosis: systematic review

 Characteristics and main results of the included studies.

ReferenceAuthor/YearDatabaseStudy objectiveSummary of results
[27]Asouri et al./2020Web of ScienceGenotyping of 14 SNPs in HLA-DRA and 14 SNPs in IL2RA by NGS in 102 Iranian MS patientsNo significant association found between the SNPs and MS
[28]Chi et al./2019PubMedGenetic mapping and ancestry analysis of HLA alleles in African American, Hispanic, and Asian populationsDifferences in MS risk were detected depending on HLA allele ancestry. European alleles DRB1*15:01, HLA-B*07:02, and HLA-A*03:01 conferred higher MS risk than their African counterparts
[29]Fguirouche et al./2025Web of ScienceGenotyping of HLA-A, -B, -DR, -DQ in healthy individuals from southern MoroccoPredisposing alleles identified: DRB1*03, *13, *15. No differences found between HLA class I alleles and MS susceptibility. Further studies in MS patients are needed
[30]Khdair et al./2025Web of ScienceGenotyping of HLA-DRB1 and HLA-DQB1 in MS patients from JordanSignificant associations found between HLA alleles and MS susceptibility: DRB1*03:01 and DRB1*04:01
[31]Beecham et al./2022PubMedAnalysis of genetic risk modified by ancestry in HLA haplotypes in a multiethnic populationSNPs rs2844503, rs3021302, and rs760145 showed effects modified by global/local ancestry. HLA-A*02:01 had a stronger protective effect when of European origin, and HLA-B*53:01 conferred protection when inherited from African origin, especially among Hispanics
[32]Goodin et al./2021PubMedAnalysis of full HLA haplotypes in African Americans with MSThe extended haplotype DRB1*15:01~DQB1*06:02 was most strongly associated with MS. The DRB1*15:03~DQB1*06:02 haplotype had a less consistent association depending on the specific haplotype
[33]Osoegawa et al./2021PubMedNGS genotyping of 11 HLA genes in families with MSAssociation found between the haplotype DRB5*01:01~DRB1*15:01 and the allele DPB1*104:01 with MS. Alleles such as DRB1*01:01 and DQB1*03:01 showed a protective effect
[34]Akel et al./2022PubMedHigh-resolution HLA class II sequencing in Swedish MS patients69 distinct genotypes detected; extended haplotypes such as DRB5*01:01~DRB1*15:01-DQB1*06:02 were more frequent; protective and risk effects depended on specific combinations
[35]Briggs and Sept/2021Web of ScienceIdentification of genetic association patterns in MS patient dataCombinations of variants such as HLA-DRB1*15:01, SNP rs56678847, and rs6880809 conferred a 20.2-fold increased risk of developing MS. Computational methods identified complex susceptibility patterns
[36]Hedström et al./2021PubMedInvestigation of gene-environment interaction (HLA and factors such as smoking, EBV, obesity)DRB1*15:01 allele increased the risk of developing MS additively, and the absence of A*02:01 increased the risk fivefold
[40]Boullerne et al./2024PubMedValidation of tagging SNPs for HLA risk alleles in MS using the 1000 genomes panelSNPs with high performance for inference of DRB1*15:01, DQB1*06:02, and A*02:01 were identified across multiple populations
[37]Barnes et al./2021PubMedAnalysis of common genetic variants in MS in Orkney and Shetland populationsSNP rs9271069 was more frequent in the islands than on the mainland and partly explained the excess MS cases
[38]Gontika et al./2020Web of ScienceGenotyping HLA-DRB1 in POMS and AOMS patientsHLA-DRB1*03 allele was significantly higher in the POMS group than in the AOMS group. In the POMS group, DRB1*11, *15, *03, *04, and *16 were identified as predisposing
[39]Derdelinckx et al./2020PubMedAnalysis of myelin antigen reactivity in MS patients with different HLA class II genotypesNo correlation found between HLA class II genotype and myelin peptide reactivity
[41]Mack et al./2019PubMedGenotyping of HLA class I and II by NGS and analysis of KIR loci and their ligandsAssociation of DRB1*15:01 with MS was confirmed. Protective haplotypes identified: C*03:04~B*40:01; A*02:01
[42]Creary et al./2019Web of ScienceHigh-resolution sequencing of DRB1*15:01 and DRB1*04:01 haplotypes in North AmericansConfirmation of DRB1*15:01~DRB5*01:01 haplotype in MS susceptibility; DRB1*04:01 had haplotype-dependent effects
[43]da Silva Bernardes et al./2019PubMedGenotyping of HLA-DR15 in familial MS cases in BrazilExtended HLA-DR15 haplotype was found in 44% of familial cases and in none of the healthy controls
[44]Asouri et al./2020Web of ScienceGenotyping of 36 SNPs located in HLA-DRA, IL2RA, and HMGB1 genes using PCR and NGSSNPs rs4935356, rs3177928, and rs7197 were considered predisposed to MS
[45]Watanabe et al./2021Web of ScienceGenotype-phenotype correlation with HLA-DRB1/DPB1 alleles in MSDRB1*15:01 was associated with susceptibility and worse prognosis in MS; DRB1*04:05 with earlier onset
[46]Ogawa et al./2019PubMedNGS genotyping of 16 HLA genes (classical and non-classical) in Japanese MS patientsDRB1*15:01, DRB1*04:05, B*15:01, and B*39:01 were independently associated with MS
[47]Burnard et al./2022Web of ScienceApplication of penalized regression (elastic net) to identify HLA and NK SNP associations with MSVariants overlooked by traditional GWAS were identified, such as SNP rs2844482
Return to article view

SNPs: single nucleotide polymorphisms; HLA: human leukocyte antigen; NGS: next-generation sequencing; MS: multiple sclerosis; EBV: Epstein-Barr virus; POMS: pediatric-onset MS (early-onset, pediatric and adolescent, MS accounts for approximately 3–5% of all MS cases); AOMS: adult-onset MS; PCR: polymerase chain reaction; NK: natural killer; GWAS: genome wide association studies.