The COMT val158met polymorphism is associated with height and cortical bone mass in early pubertal girls
Eriksson AL1,2,6, Suuriniemi M3,4,6, Mahonen A5,6, Cheng S3,6, Ohlsson C1,2,6
1Center for Bone Research at the Sahlgrenska Academy and 2Division of Clinical Pharmacology, Dept. of Internal Medicine, The Sahlgrenska Academy at Gothenburg University, Goteborg, Sweden,
3Department of Health Sciences and 4Department of Cell Biology, University of Jyväskylä, Jyväskylä, Finland,
5Department of Medical Biochemistry, University of Kuopio, Kuopio, Finland
6The Calex-study Research Group
ABSTRACT
Introduction: Estrogens are involved in the accretion of bone mass during puberty. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. There is a functional polymorphism in the fourth exon of the COMT gene (val158met), resulting in a 3-4 fold lower activity of the enzyme (low activity = L). The aim of the present study was to investigate the influence of this polymorphism on the skeleton in pre/early pubertal girls.
Methods: 246 healthy pre/early pubertal girls were genotyped and the individuals were classified as COMTLL, COMTHL or COMTHH. The associations between COMT genotype, skeletal phenotypes and hormone levels were investigated.
Results: Girls homozygous for the low activity COMT genotype, COMTLL, were 5.4 cm taller than individuals with COMTHH. The COMTLL individuals also had more lean mass than COMTHH while fat mass did not differ between the groups. Dual X-ray absorptiometry (DXA) measurements showed higher values of bone mineral content (BMC), and larger areas of total body, femur neck, total femur and spine in COMTLL. Cortical BMC, as measured by peripheral quantitative computerized tomography (pQCT) in the diaphyseal region of the tibia, was 9.7% higher in COMTLL compared with COMTHH. This difference was due to a larger cortical cross sectional area while the cortical volumetric BMD (vBMD) was not affected. The periosteal circumference was larger in COMTLL, suggesting that the effects on cortical cross sectional area were caused by an increased radial cortical bone growth. No effect was seen on trabecular vBMD. The COMTLL genotype had higher serum levels of free estradiol and insulin like growth factor (IGF-1). Statistical regression models indicated that the effects of COMT genotype on skeletal parameters were exerted mainly via a regulation of free estradiol.
Conclusions: We propose that a low activity COMT genotype results in elevated levels of free estradiol, which in turn results in increased longitudinal and cortical radial bone growth in pre/early pubertal girls.
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