Polymorphisms in the aromatase gene predict areal BMD as a result of affected cortical bone size: the GOOD study.
The association between aromatase gene polymorphisms, bone parameters, and sex steroid levels was studied in 1068 men (18.9 +/- 0.6 years of age). Several aromatase gene polymorphisms were found to be associated with serum testosterone levels and cortical bone size but not with trabecular volumetric BMD.


BACKGROUND
Both testosterone and estrogens are important for the male skeleton. Aromatase, the product of the CYP19 gene, is the key enzyme in the conversion of testosterone to estradiol. A functional aromatase enzyme has been shown to be crucial for the normal development of the male skeleton. The role of genetic polymorphisms in the aromatase gene for trabecular volumetric BMD (vBMD) and cortical bone size has not previously been studied in men.


METHODS
The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (18.9 +/- 0.6 years of age). The TTTA repeat polymorphism (TTTAn) and three single nucleotide polymorphisms (SNPs), including the Val80 SNP, in the CYP19 gene, were analyzed. Serum levels of testosterone and estradiol were measured. Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular vBMD and cortical bone size were measured by pQCT.


RESULTS
The TTTAn and the Val80 genotypes were independent predictors of aBMD of the radius, lumbar spine, total body, and cortical bone size (cortical cross-sectional area and thickness) of both the radius and tibia. In contrast, trabecular vBMD was not associated with CYP19 polymorphisms. Homozygosity for the long allele (>9 repeats) of the TTTAn and for the G allele of the Val80 SNP was associated with the highest aBMD and testosterone levels as well as with the greatest cortical bone size. Regression analyses indicated that the association with aBMD was mediated through affected cortical bone size.


CONCLUSIONS
We showed, in a large well-characterized cohort of men at the age of peak bone mass, that several common aromatase polymorphisms are associated with cortical bone size but not with trabecular vBMD. One may speculate that affected CYP19 activity, resulting in altered testosterone levels during pubertal development, might contribute to the association between CYP19 polymorphisms and cortical bone size.
Lorentzon
Mattias
M
Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Gothenburg University, Gothenburg, Sweden. mattias.lorentzon@medic.gu.se
Swanson
Charlotte
C
Eriksson
Anna-Lena
AL
Mellström
Dan
D
Ohlsson
Claes
C
D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D001141:Aromatase / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000378:metabolism; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013739:Testosterone / Q000097:blood*
D013739:Testosterone; D004958:Estradiol; D001141:Aromatase