The COMT val158met polymorphism is associated with early pubertal development, height and cortical bone mass in girls.
Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60-75% difference in enzyme activity between the val (high activity = H) and the met (low activity = L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4 cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT(LL). Cortical BMC, measured by peripheral quantitative computerized tomography in the tibia, was 9.8% higher in COMT(LL) compared with COMT(HH). This was due to a larger cortical cross sectional area while the cortical volumetric bone mineral density was not associated with COMT genotype. COMT(LL) girls had higher serum levels of free estradiol and insulin like growth factor. Regression models indicated that COMT genotype exerted effects on skeletal growth mainly via a regulation of free estradiol, resulting in an affected pubertal development (Tanner staging). We propose that the COMT(LL) genotype results in higher free estradiol levels and earlier pubertal development, leading to an increased skeletal growth in pre/early pubertal girls. Possible consequences for the adult skeleton however can be determined only after cessation of growth.
Center for Bone Research at Sahlgrenska Academy, Division of Clinical Pharmacology, Dept. of Internal Medicine, Göteborg University, SE-413 45 Göteborg, Sweden.
Anna-Lena
AL
Eriksson
Miia
M
Suuriniemi
Anitta
A
Mahonen
Sulin
S
Cheng
Claes
C
Ohlsson
D015502:Absorptiometry, Photon; D001823:Body Composition; D001827:Body Height; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008715:Methionine / Q000737:chemistry*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011627:Puberty / Q000235:genetics*; D012044:Regression Analysis; D014057:Tomography, X-Ray Computed; D014633:Valine / Q000737:chemistry*
D004967:Estrogens; D004958:Estradiol; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine