Estrogen receptor alpha in giant cell arteritis: a molecular genetic study.
OBJECTIVE
Giant cell arteritis (GCA) predominantly affects postmenopausal women. Estrogen receptor alpha (ER alpha) accumulates in the cytoplasm of smooth muscle cells, activated mononuclear inflammatory cells and giant cells in the temporal arteries of GCA patients, as well as in smooth muscle cells in arteries from non-GCA controls. The aim of this study was to analyse whether this accumulation is related to structural aberrations in the ER alpha mRNA leading to a change in protein structure.


METHODS
Total RNA was extracted from inflamed temporal artery tissue in two GCA patients and from non-inflamed arteries in two non-GCA controls. Products from the nested RT-PCR of the cDNA were cloned and plasmid inserts of 20 different clones from each case were investigated using nucleotide sequence analysis.


RESULTS
A total of eight different types of transcripts lacking parts of the ER alpha mRNA were detected. Seven of these could be explained by alternative splicing. There were no significant differences between the GCA patients and the non-GCA controls in terms of the number of transcript variants.


CONCLUSIONS
The accumulated cytoplasmic ER alpha in temporal arterial tissue from elderly persons appears mainly to be of wild type. The main structural changes in the ER alpha mRNA may be due to alternative splicing. Somatic mutations of the ER alpha gene appear to be rare and it is therefore unlikely that they are involved in the pathogenesis of GCA.
Petursdottir
V
V
Department of Pathology, University of Iceland, Reykjavik, Iceland. vigpet@rsp.is
Moslemi
A R
AR
Persson
M
M
Nordborg
E
E
Nordborg
C
C
D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D004252:DNA Mutational Analysis; D047628:Estrogen Receptor alpha; D005091:Exons; D005260:Female; D013700:Giant Cell Arteritis / Q000235:genetics*; D006801:Humans; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics*
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen