|(C;T)||1.8||3x higher risk of multiple sclerosis|
|(T;T)||2||3-6x higher risk of multiple sclerosis|
rs3135388(T) is highly (> 99%) correlated with the HLA-DRB1*1501 allele; the risk allele (T) is associated with a 3 to 6 fold higher risk for developing multiple sclerosis. [PMID 17660530] The risk per allele (or per haplotype) appears additive. [PMID 11424637] It has also been associated with other autoimmune diseases, such as systemic lupus erythematosis (SLE) (see) and, when linked with DQB1*0602, narcolepsy.
The HLA-DRB1*1501 allele is fairly common; for example, it occurs in 15-30% of individuals of Northern European ancestry. Note: most publications refer to the risk allele as rs3135388(A), but in dbSNP and SNPedia orientation, it is rs3135388(T).
An interesting series of correlations have been woven together to suggest that a possible way to lower the risk of rs3135388(T) carriers developing multiple sclerosis would be to ensure sufficient vitamin D production, presumably through sunlight exposure, during as yet unknown critical periods in development. 10.1371/journal.pgen.1000369
|Title||Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci|
|Odds Ratio||2.75 [2.46-3.07]|
[PMID 20591987] HLA DRB1*1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica
[PMID 21067287] Multiple sclerosis risk markers in HLA-DRA, HLA-C, and IFNG genes are associated with sex-specific childhood leukemia risk
[PMID 21816760] Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis
[PMID 22363536] DRB1*03:01 Haplotypes: Differential Contribution to Multiple Sclerosis Risk and Specific Association with the Presence of Intrathecal IgM Bands
[PMID 18647361] A Taqman assay for high-throughput genotyping of the multiple sclerosis-associated HLA-DRB1*1501 allele.
[PMID 18941528] Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms.
[PMID 19387463] Variation in the ATP-binding cassette transporter 2 gene is a separate risk factor for systemic lupus erythematosus within the MHC.
[PMID 20007504] Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci.
[PMID 20008659] HLA-DRB1*1501 and spinal cord magnetic resonance imaging lesions in multiple sclerosis.
[PMID 20335276] PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.
[PMID 20369022] Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations.
[PMID 20405052] The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.
[PMID 20593013] A major histocompatibility Class I locus contributes to multiple sclerosis susceptibility independently from HLA-DRB1*15:01.
[PMID 21304891] A study of CNVs as trait-associated polymorphisms and as expression quantitative trait loci.
[PMID 21570397] Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.
[PMID 22253788] Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.
[PMID 22411505] Replication study of multiple sclerosis (MS) susceptibility alleles and correlation of DNA-variants with disease features in a cohort of Austrian MS patients.
[PMID 23186557] Association of HLA-DRB1*1501 tagging rs3135388 gene polymorphism with multiple sclerosis
[PMID 23834030] Polymorphisms in HLA-related genes and psoriasis heredity in patients with psoriasis
[PMID 23840333] Vitamin D3 Receptor ( VDR ) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis
[PMID 22492128] Association of SNPs rs6498169 and rs10984447 with multiple sclerosis in Saudi patients: a model of the usefulness of familial aggregates in identifying genetic linkage in a multifactorial disease.
[PMID 23379431] Serum concentration of immunoglobulin G-type antibodies against the whole Epstein-Barr nuclear antigen 1 and its aa35-58 or aa398-404 fragments in the sera of patients with systemic lupus erythematosus and multiple sclerosis.
[PMID 25958306] VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks
[PMID 26011527] Combinations of Susceptibility Genes Are Associated with Higher Risk for Multiple Sclerosis and Imply Disease Course Specificity
[PMID 26865406] Multiple sclerosis in families: risk factors beyond known genetic polymorphisms.
[PMID 29379819] Elevated EBNA-1 IgG in MS is associated with genetic MS risk variants.
[PMID 29532745] Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis.