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rs3135388

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(C;C) 0 normal
(C;T) 1.8 3x higher risk of multiple sclerosis
(T;T) 2 3-6x higher risk of multiple sclerosis
ReferenceGRCh38 38.1/141
Chromosome6
Position32445274
GeneHLA-DRA
is asnp
is mentioned by
dbSNPrs3135388
ebirs3135388
HLIrs3135388
Exacrs3135388
Varsomers3135388
Maprs3135388
PheGenIrs3135388
hapmaprs3135388
1000 genomesrs3135388
hgdprs3135388
ensemblrs3135388
gopubmedrs3135388
geneviewrs3135388
scholarrs3135388
googlers3135388
pharmgkbrs3135388
gwascentralrs3135388
openSNPrs3135388
23andMers3135388
23andMe allrs3135388
SNP Nexus

SNPshotrs3135388
SNPdbers3135388
MSV3drs3135388
GWAS Ctlgrs3135388
GMAF0.06428
Max Magnitude2
? (C;C) (C;T) (T;T) 28
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

[PMID 19433080] Association between rs3135388(T) allele and multiple sclerosis also seen in 269 Serbian patients, with an odds ratio of 2 for (T) allele carriers.

GWAS snp
PMID [PMID 19525953OA-icon.png]
Trait Multiple sclerosis
Title Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci
Risk Allele A
P-val 0
Odds Ratio 2.75 [2.46-3.07]
OMIM126200
DescMULTIPLE SCLEROSIS, SUSCEPTIBILITY TO; MS
Variant
Relatedalso
OMIM142857
DescMAJOR HISTOCOMPATIBILITY COMPLEX, CLASS II, DR BETA-1; HLA-DRB1
Variant
Relatedalso
OMIM142860
DescMAJOR HISTOCOMPATIBILITY COMPLEX, CLASS II, DR ALPHA; HLA-DRA
Variant
Relatedalso


[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 22363536OA-icon.png] 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 18941528OA-icon.png] 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 19387463OA-icon.png] Variation in the ATP-binding cassette transporter 2 gene is a separate risk factor for systemic lupus erythematosus within the MHC.


[PMID 20007504OA-icon.png] 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 20335276OA-icon.png] PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.


[PMID 20369022OA-icon.png] Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations.


[PMID 20405052OA-icon.png] The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.


[PMID 20593013OA-icon.png] A major histocompatibility Class I locus contributes to multiple sclerosis susceptibility independently from HLA-DRB1*15:01.


[PMID 21304891OA-icon.png] A study of CNVs as trait-associated polymorphisms and as expression quantitative trait loci.


[PMID 21570397OA-icon.png] Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.


[PMID 22253788OA-icon.png] 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.


GET Evidence
rs3135388
aa_change
aa_change_short
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.921875
summary



[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 23840333OA-icon.png] 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 23379431OA-icon.png] 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 26011527OA-icon.png] 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.