GENETIC AND ENVIRONMENTAL COMPONENTS OF INTERINDIVIDUAL VARIATION IN CIRCULATING LEVELS OF IGF-I, IGF-II, IGFBP-1, AND IGFBP-3

We assessed the magnitude of the genetic component in the variation of circulating levels of insulin-like growth factors I and II (IGF-I and IGF-II), and their binding proteins IGFBP-1 and IGFBP-3 by measuring their serum concentrations in 32 monozygotic and 47 dizygotic adult tw in pairs of the same sex. The intrapair correlation for the IGF-I leve ls was r = 0.41 (P < 0.009) for monozygotic twins and r = 0.12 (P < 0. 22) for dizygotic twins. For the IGF-II concentration the intrapair co rrelations were r = 0.66 (P < 0.0001) for the monozygotic and r = 0.34 (P < 0.01) for the dizygotic twins. No significant intrapair correlat ion was found for IGFBP-1 levels in either group. The correlations for IGFBP-3 concentration were r = 0.65 (P < 0.0001) and r = 0.23 (P < 0. 06) for monozygotic and dizygotic twins, respectively. Women had highe r IGF-II levels than men (635 +/- 175 vs. 522 +/- 144 mu g/liter; P < 0.0001) and IGFBP-3 levels were also higher in women compared with men (5441 +/- 1018 vs. 4496 +/- 1084 mu g/ liter; P < 0.001). The proport ion of variance attributable to genetic effects was 38% for the IGF-I concentration, 66% for the IGF-II concentration, and 60% for the IGFBP -3 concentration. No significant heritability was found for the IGFBP- 1 concentrations. Our results show that, in adults, there is a substan tial genetic contribution responsible for interindividual, variation o f the circulating levels of IGF-I, IGF-II, and IGFBP-3, but not for th e IGFBP-1 levels.