Association between androgen receptor gene CAG repeat polymorphism and plasma testosterone levels in postmenopausal women.
OBJECTIVE
The biologic action of androgens in target cells depends on plasma androgen levels and receptor transcriptional activity. We investigated the relationship between androgen receptor (AR) CAG repeat polymorphism, serum androgen levels, and anthropometric, metabolic, and hormonal variables in 39 postmenopausal women, taking into consideration the patterns of X-chromosome inactivation.


METHODS
Genomic DNA was extracted from peripheral leukocytes. Polymerase chain reactions (PCRs) were performed to amplify the polymorphic (CAG)n repeat of the human AR gene, which were analyzed with GeneScan software (Applied Biosystems, Foster City, CA). The X-chromosome inactivation analysis was based on the AR gene methylation patterns.


RESULTS
The mean age of participants was 54.7 years; mean age at menopause was 48 years. The number of CAG repeats ranged from 15 to 30, with a median length of 23. Analysis of X-chromosome inactivation patterns showed 19 cases with a degree of skewing (DS) > or =70% and seven with a DS > or =90%. The X-weighted CAG repeat biallelic mean was significantly lower in individuals with total testosterone (TT) greater than 0.56 ng/mL (group mean) than in the group with TT < or =0.56 (P=.018). No difference was observed between the groups regarding dehydroepiandrosterone sulfate (DHEA-S). Plasma TT was significantly higher in the group with the smaller X-weighted CAG repeat biallelic mean (P=.01). Free androgen index (FAI) was also significantly higher in this group (P=.033). Testosterone levels and FAI were inversely correlated to X-weighted CAG repeat biallelic mean.


CONCLUSIONS
Our data indicate an association between testosterone plasma levels and AR CAG repeats in postmenopausal women, and suggest that plasma levels of androgens in postmenopausal women may be related to variants of the AR gene.
Brum
Ilma Simoni
IS
Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. ilma@ufrgs.br
Spritzer
Poli Mara
PM
Paris
Françoise
F
Maturana
Maria Augusta
MA
Audran
Françoise
F
Sultan
Charles
C
D000483:Alleles; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D041321:Chromosomes, Human, X / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood* / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D018911:Trinucleotide Repeats
D001786:Blood Glucose; D007328:Insulin; D011944:Receptors, Androgen; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA