Nuclear receptor coactivator-3 alleles are associated with serum bioavailable testosterone, insulin-like growth factor-1, and vertebral bone mass in men.
BACKGROUND
Nuclear receptor coactivator-3 (NCOA3) is a member of the steroid receptor coactivator family that interacts with nuclear hormone receptors to enhance their transcriptional activation function and may play a role in somatic growth.


OBJECTIVE
The aim of this study was to examine the relationships between the CAG/CAA (glutamine) length variation at the NCOA3 locus, sex steroid hormone, and IGF-I levels and bone mineral density (BMD) in a cohort of older Caucasian men.


METHODS
We analyzed the association between potentially functional alleles at this locus, serum sex steroid hormone, and IGF-I levels and lumbar spine and proximal femur BMD (Hologic QDR) in 263 community-dwelling Caucasian men (age 66 +/- 7 yr, mean +/- sd; range 51-84 yr). Men were genotyped for a CAG/CAA repeat polymorphism in NCOA3, which encodes a polyglutamine tract of variable length in the C-terminal transcriptional activation domain of the protein.


RESULTS
We found a significant monotonic decrease in lumbar spine, but not hip, BMD with increasing copies of the most common allele (29 repeats, 53%). For example, men with the 29/29 genotype had 6% or nearly 0.5 sd lower spine BMD than men without this genotype, and NCOA3 genotype explained 3.2% of the phenotypic variation in this trait. Serum levels of bioavailable testosterone and IGF-I paralleled genotype-related differences in lumbar spine BMD.


CONCLUSIONS
Allelic variation at the NCOA3 locus may contribute to the genetic control of androgenic hormone and IGF levels and vertebral bone mass among older men.
Sheu
Yah-Tyng
YT
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Zmuda
Joseph M
JM
Cauley
Jane A
JA
Moffett
Susan P
SP
Rosen
Clifford J
CJ
Ishwad
Chandra
C
Ferrell
Robert E
RE
D000123:Acetyltransferases / Q000235:genetics*; D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics; D015331:Cohort Studies; D005838:Genotype; D005973:Glutamine / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000097:blood; D051548:Histone Acetyltransferases; D006728:Hormones / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins / Q000235:genetics*; D009929:Organ Size / Q000502:physiology; D013131:Spine / Q000033:anatomy & histology*; D013739:Testosterone / Q000097:blood*; D015534:Trans-Activators / Q000235:genetics*; D018911:Trinucleotide Repeats
D012739:Gonadal Steroid Hormones; D006728:Hormones; D015513:Oncogene Proteins; D015534:Trans-Activators; D005973:Glutamine; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3