Analysis of G/A polymorphism in the androgen response element I of the PSA gene and its interactions with the androgen receptor polymorphisms.
OBJECTIVE
To compare the in vitro functional activity of the prostate-specific antigen (PSA) androgen response element (ARE) I alleles alone or in combination with androgen receptor (AR) polymorphisms and to determine the association of ARE I alleles with serum PSA in men without clinical prostatic disease. Data are conflicting regarding the association of PSA promoter alleles with serum PSA in men.


METHODS
In vitro functional analyses of ARE I and AR polymorphisms were conducted by luciferase reporter assays in LNCaP and PC-3 cells. Associations among serum PSA, ARE I, and AR genotypes were determined by genotyping 109 white and 71 African-American men determined to be free of clinical prostatic disease.


RESULTS
We found no significant difference in the androgen responsiveness of the two alleles when cells were transfected with PSA promoter reporter constructs differing only in the ARE I single nucleotide polymorphism and treated with varying doses of androgen. The response to androgens of the ARE I alleles co-transfected with AR expression vectors of 9, 21, and 29 CAG repeat lengths were identical. No individual or combined effects of the ARE I genotype and the AR genotype on serum PSA were noted.


CONCLUSIONS
Our data indicate that ARE I polymorphisms, alone or in combination with AR polymorphisms, have no functional effect on the activity of the PSA promoter in vitro and in vivo.
Rao
Anuradha
A
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Chang
Bao-L i
BL
Hawkins
Gregory
G
Hu
Jennifer J
JJ
Rosser
Charles J
CJ
Hall
M Craig
MC
Meyers
Deborah A
DA
Xu
Jianfeng
J
Cramer
Scott D
SD
D000328:Adult; D000368:Aged; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010173:Palpation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D014162:Transfection; D018911:Trinucleotide Repeats / Q000235:genetics
D011944:Receptors, Androgen; D008156:Luciferases; D017430:Prostate-Specific Antigen