This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.
Using a logistic regression model, two SNPs (MHC Class III SNP rs422951 in the NOTCH4 gene and MHC Class II SNP rs3997849, susceptible alleles A and G, respectively) were independently associated with MS susceptibility (204 patients; 280 controls), two (MHC Class II SNP rs660895 and MHC Class I SNP rs2269704 in the NRM gene, susceptible alleles G and G, respectively) with aquaporin-4- (AQP4-) MS susceptibility (149 patients; 280 controls) and a single SNP (MHC Class II SNP rs1694112, susceptible allele G) was significant when contrasting AQP4+ against AQP4- patients.
We conclude that alleles of the NOTCH4 and TNFalpha genes are unlikely to be of importance for the susceptibility to MS, although specific alleles of these genes are often carried on the same haplotype as DR15, DQ6.