Notch4, a non-HLA gene in the MHC is strongly associated with the most severe form of alopecia areata

Alopecia areata (AA) is a disorder primarily affecting the hair and nails in which associated autoimmune or atopic disease is common. Genetically, it is a complex trait with evidence of a role for genes of the major histocompatibility complex (MHC), the interleukin-1 cluster and chromosome 21 in the...

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Bibliographic Details
Published in:Human genetics 2003-04, Vol.112 (4), p.400-403
Main Authors: Tazi-Ahnini, R, Cork, M J, Wengraf, D, Wilson, A G, Gawkrodger, D J, Birch, M P, Messenger, A G, McDonagh, A J G
Format: Article
Language:English
Subjects:
Alleles
Alopecia
Alopecia Areata - diagnosis
Alopecia Areata - genetics
Baldness
Case-Control Studies
Genes
Genetic aspects
Genetic engineering
Genetic polymorphisms
Genetic research
Genotype
Humans
Medical research
Medicine, Experimental
Odds Ratio
Polymorphism, Genetic
Proto-Oncogene Proteins - genetics
Receptor, Notch4
Receptors, Cell Surface
Receptors, Notch
Severity of Illness Index
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Summary:Alopecia areata (AA) is a disorder primarily affecting the hair and nails in which associated autoimmune or atopic disease is common. Genetically, it is a complex trait with evidence of a role for genes of the major histocompatibility complex (MHC), the interleukin-1 cluster and chromosome 21 in the pathogenesis. The strongest association is with HLA class II alleles, although whether this indicates a direct contribution to the pathogenesis or results merely from linkage disequilibrium with nearby disease genes is unknown. Notch4 is a recently defined gene in the HLA class III region. Notch signalling is a direct determinant of keratinocyte growth arrest and entry into differentiation. A possible role for Notch in hair growth has been indicated by transgenic mouse findings that activation of the Notch pathway in the hair cortex leads to aberrant differentiation of adjacent hair-shaft layers. Notch4 is therefore a plausible candidate gene for AA. We have examined two polymorphisms in the coding sequence of the Notch4 gene at positions +1297 and +3063 in a case-control study of 116 AA patients and 142 ethnically matched, healthy control subjects. The initial analysis showed a significant association of AA in the overall data set with the Notch4(T+1297C) polymorphism (P
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-002-0898-9