Multiple sclerosis
Multiple sclerosis (MS) is thoiught to be an autoimmune disease in which a person's immune system damages the central nervous system, causing a wide variety of symptoms, including difficulties moving. It is the most common neurologic disease affecting young adults. Wikipedia has an excellent overview.
Most SNPs associated with MS are located in genes playing roles in the immune system. The main allele implicated to date is known as HLA-DRB1*1501, a Class II member of the major histocompatibility complex (MHC). An HLA-DRB1 SNP that is highly correlated with HLA-DRB1*1501, and thus multiple sclerosis, is rs3135388. A recent hypothesis is that a possible way to reduce the frequency 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 Another SNP that tags the HLA-DRB1*1501 allele is rs3135391. [PMID 20593013]
Researchers in the UK and Canada suspect that mutations in the CYP27B1 gene lead to development of multiple sclerosis, suggesting that deficiency of vitamin D is involved. BBC News
A study of ~2,300 patients has also reported that SNPs from other HLA regions, most notably rs4959039, can be shown to increase risk for multiple sclerosis regardless of HLA-DRB1*1501 status. [PMID 20593013]
An algorithm has been developed combining 16 SNPs that appears to "modestly predict" multiple sclerosis risk. [PMID 19879194] A more recent study combining known MS SNPs concludes that prediction of MS "cannot be achieved with the currently available genetic data." [PMID 21280076]
Less pronounced yet still statistically significant increased risk has been reported for the following SNPs [PMID 17660530]:
- rs10492972, in the KIF1B gene
- rs12722489 and rs2104286, both located in intron 1 of the IL2RA gene;
- rs6897932, located in the coding region of the IL7RA gene [PMID 17660530]
- rs6498169, in the KIAA0350 gene
- rs6604026, in the RPL5 gene
- rs10984447, in the DBC1 gene
- rs12044852, in the CD58 gene
- rs7577363, in the ALK gene
- rs7536563 and rs11164838, in the FAM69A gene
- rs10975200, in the ANKRD15 gene
- rs10735781 and rs6680578, in the EVI5 gene
- rs4763655, in the KLRB1 gene
- rs12487066, in the CBLB gene
- rs1321172, in the PDE4B gene
Additional SNPs (from other studies) include:
- rs870849, a SNP in the lymphocyte activation gene LAG3
- rs8702, a protective SNP in the KLC1 gene
- rs926103 and a GA repeat polymorphism forming a risk haplotype in Norwegian patients [PMID 18554728]
- rs12708716 and rs2041670, in the CLEC16A gene
- rs763361, in the CD226 gene
- rs1800693 and rs4149584, in the TNFRSF1A gene [PMID 19525953]
- rs17445836, near the IRF8 gene
- rs11117432, in the IRF8 gene [PMID 19525953]
- rs2300747, in the CD58 gene [PMID 19525953]
- rs17824933 and rs929230, in the CD6 gene
- rs3135388, mentioned above [PMID 19525953]
- rs12722561, a protective allele at the IL2RA locus [PMID 17660530]
[PMID 18285424] rs4728142, rs3807306 and a 5 bp insertion-deletion linked multiple sclerosis in three populations
spittoon
Variant Nearest Gene Version Odds Ratio
rs1738074 TAGAP T 0.88 rs669607 None C 1.15 rs1077667 TNFSF14 T 0.88 rs17066096 IL22RA2 G 1.14 rs11154801 MYB A 1.09 rs4902647 ZFP36L1 T 0.88 rs7595037 PLEK G 0.87 rs2248359 CYP24A1 T 0.90 rs2546890 IL12B G 0.87 rs9282641 CD86 A 0.83
