Investigation of NOTCH4 coding region polymorphisms in sporadic inclusion body myositis.
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.
School of Pathology and Laboratory Medicine, M504, University of Western Australia, Stirling Highway, Nedlands 6009, Perth, Australia. ascott@mmri.mater.org.au
Adrian P
AP
Scott
Nigel G
NG
Laing
Frank
F
Mastaglia
Marinos
M
Dalakas
Merrilee
M
Needham
Richard J N
RJ
Allcock
D000483:Alleles; D015331:Cohort Studies; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018979:Myositis, Inclusion Body / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics*
D005819:Genetic Markers; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch