Quantitative genetic analysis of circulating levels of biochemical markersof bone formation

Carboxyterminal propeptide of type 1 collagen (PICP) and bone G1a-protein-o steocalcin (BGP) are the most important components of the organic bone matr ix and play a key role in bone formation. To investigate whether and to wha t extent variation of the plasma levels of these indices of bone turnover d epends on genetic factors, we studied 355 adults belonging to nuclear pedig rees, Genetic analysis was carried out in 2 steps: 1) variance decompositio n analysis was performed using the FISHER statistical package; and 2) compl ex segregation analysis implemented in the program package MAN. The effect of age and gender differences, gender hormones, as well as PTH and vitamin- D (calcidiol) plasma levels were evaluated simultaneously with the paramete rs of variance analysis, The results showed that about 50% of PICP variatio n is attributable to genetic factors. The effect of age was significant amo ng men and postmenopausal women, whereas calcidiol influenced variation of PICP in premenopausal women, The results of variance analysis showed that s ome 40% of BGP, adjusted for confounding variables, can be explained in gen etic factors, Age and PTH were important covariates for osteocalcin in men and premenopausal women. Exploration of the maximum likelihood estimates of the various hypotheses concerning the mode of intergenerational transmissi on of PICP and BGP demonstrated a good correspondence to the Mendelian mode of inheritance (i.e., major gene effect). Am. J. Med. Genet. 94:324-331, 2 000. (C) 2000 Wiley-Liss, Inc.