Association between androgen receptor gene polymorphism and bone density in older women using hormone replacement therapy.
OBJECTIVE
The objective of this study was to investigate the relationship between bone mineral density (BMD) and both CAG repeat polymorphism of the androgen receptor (AR) gene and skewed X chromosome inactivation (SI) in postmenopausal women.


METHODS
BMD was measured by DEXA. Both the number and the X-weighted biallelic mean of the CAG repeats of AR were analysed by PCR, before and after DNA digestion with methylation-sensitive HpaII in 192 healthy Caucasian postmenopausal women.


RESULTS
The number of CAG repeats ranged from 10 to 34, with a median value of 22. CAG)(n< or =22) and CAG)(n> or =23) alleles were designated as short and long alleles, respectively. In women using hormone replacement therapy (HRT) (n=81), lumbar spine BMD was significantly lower, and femoral neck and total body BMD marginally lower in those with long-long alleles when compared with those with other genotypes. SI (> or =80%) was observed in 24% of the women and was not associated with BMD. In women using HRT, femoral neck BMD was significantly lower, and lumbar spine and total body BMD marginally lower in those whose X-weighted CAG repeat biallelic was greater than 22.59 (median value) when compared to other genotypes. These results were not found in women not using HRT.


CONCLUSIONS
In conclusion, our results suggest that BMD may be associated with AR gene polymorphism in postmenopausal women using HRT but not with SI. Further studies are needed to investigate the mechanisms of the interaction between HRT, BMD and AR found in the present study.
Retornaz
Fréderique
F
Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France.
Paris
Françoise
F
Lumbroso
Serge
S
Audran
Françoise
F
Tigoulet
Fabien
F
Michelon
Cécile
C
Jeandel
Claude
C
Sultan
Charles
C
Blain
Hubert
H
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D005260:Female; D050172:Genes, X-Linked; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018911:Trinucleotide Repeats; D049951:X Chromosome Inactivation
D011944:Receptors, Androgen; D004247:DNA; C029641:DNA modification methylase HpaII; D015257:DNA-Cytosine Methylases