The NOTCH4 gene, located within the MHC region, is involved in cellular differentiation and has varying effects dependent on tissue type. Coding region polymorphisms haplotypic of the sIBM-associated 8.1 ancestral haplotype were identified in NOTCH4 and genotyped in two different Caucasian sIBM cohorts. In both cohorts the frequency of the minor allele of rs422951 and the 12-repeat variation for rs72555375 was increased and was higher than the frequency of the sIBM-associated allele HLA-DRB1*0301. These NOTCH4 polymorphisms can be considered to be markers for sIBM susceptibility, but require further investigation to determine whether they are directly involved in the disease pathogenesis.
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