Mutations in the human 5-lipoxygenase gene.
Our data demonstrate the presence of a naturally occurring family of alleles in the core promoter of the 5-LO gene, which is characterized by the deletion or addition of consensus Sp1 (-GGGCGG) and Egr-1 (-GCGGGGGCG-) binding motifs. Each of the variant alleles can bind Sp1 and Egr-1 protein, as indicated by EMSA and supershift analysis with nuclear extracts. In addition, preliminary data from CAT reporter assays indicate that these alleles are less effective than the wild-type allele in initiating 5-LO gene expression. Whether patients harboring the various alleles identified herein have different capacities to transcribe the 5-LO gene and the importance of such potential regulation to the clinical expression of 5-LO have yet to be determined.
In
K H
KH
Department of Medicine, Brigham and Women's Hospital, Boston, MS, USA.
Silverman
E S
ES
Asano
K
K
Beier
D
D
Fischer
A R
AR
Keith
T P
TP
Serino
K
K
Yandava
C
C
De Sanctis
G T
GT
Drazen
J M
JM
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000483:Alleles; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001249:Asthma / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005260:Female; D017930:Genes, Reporter; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D020121:5' Untranslated Regions; D014157:Transcription Factors; D001094:Arachidonate 5-Lipoxygenase; D015500:Chloramphenicol O-Acetyltransferase