Nuclear receptor coactivator-3 alleles are associated with serum bioavailable testosterone, insulin-like growth factor-1, and vertebral bone mass in men.
Document Type
Article
Publication Date
2006
Keywords
Aged, Alleles, Bone-Density, Cohort-Studies, Genotype, Glutamine, Gonadal-Steroid-Hormones, Hormones, Humans, Insulin-Like-Growth-Factor-I, Male, Middle-Aged, Oncogene-Proteins, Organ-Size, Research-Support-N, I, H, -Extramural, Spine, Testosterone, Trans-Activators, Trinucleotide-Repeats
First Page
307
Last Page
312
JAX Source
J Clin Endocrinol Metab 2006 Jan; 91(1):307-12.
Abstract
CONTEXT: 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. DESIGN AND 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. CONCLUSION: 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.
Recommended Citation
Sheu YT,
Zmuda JM,
Cauley JA,
Moffett SP,
Rosen CJ,
Ishwad C,
Ferrell RE.
Nuclear receptor coactivator-3 alleles are associated with serum bioavailable testosterone, insulin-like growth factor-1, and vertebral bone mass in men. J Clin Endocrinol Metab 2006 Jan; 91(1):307-12.